Second Opinion

Stem cell research and regenerative medicine is a complex and fast-changing field. It can sometimes seem impossible to separate the hope from the hype.

Our experts are here to give a Second Opinion on the headlines.

Second Opinion

"A new milestone in laboratory grown human brain tissue"
( )

What do our experts say?

WideCells CSO Peter Hollands looks at how stem cells are helping to power the next generation of disease study:

Quite a step forward here for the development of treatments of diseases caused by defects relating to myelin, a substance which forms the insulation of the brain. Among other things, this includes multiple sclerosis.

It focuses on an advancement in the generation of organoids, effectively tiny pieces of human tissue – usually no more than one or two millimetres in diameter – which allow us to study the causes of diseases and to test treatments, without involving human test subjects.

Organoids are created using induced pluripotent stem cells (iPSCs), a type of cell capable of making almost any human tissue. However, up till now is that we have had difficulty generating organoids which include the type of cell which generates myelin (known as ‘oligendrocytes’).

According to this report, at least one group of researchers have overcome this difficulty, enabling us to effectively have a fully functional piece of neuronal brain tissue, myelin included, for study. That means we should be able to model the degeneration and repair of myelin in the lab, giving us a significant advantage when developing and testing treatments for diseases such as MS.

This is excellent news for sufferers of myelin-based diseases, but also helps to demonstrate the potential of iPSCs in creating organoids for the study of disease more broadly. The organoid technique is likely to be used to study and better understand the vast majority of diseases is eventually, and this report stands as another encouraging piece of evidence demonstrating iPSCs’ efficacy in helping to achieve this.

Second Opinion

"Experts warn on proliferation of dubious stem cell clinics"
(Financial Times)

What do our experts say?

New US legislation means it will be easier for Americans to undergo experimental treatments – but, as WideCells CSO Peter Hollands warns, the risks are significant:

New US legislation titled the ‘Right to Try’ means that seriously ill patients will have greater access to experimental treatments. At first blush, this might seem like a good idea – but there is the potential for it to cause serious problems for both vulnerable people and the scientific and clinical community.

As the article notes, there is a preponderance of stem cell clinics specialising in misleading or outright fraudulent claims. Stem cell treatments are a magnet for fraudsters in large part because of their much publicised potential, but relatively small number of proven, routine treatments (the only treatments in regular clinical use currently are those for blood disorders). The term ‘clinical trial’ is often used by fraudulent clinics, but these ‘studies’ tend to be financially motivated – not performed with the aim of proving or disproving a treatment’s efficacy, as is the case with genuine scientific trials. Big money is at stake – often in excess of £100,000 per treatment is charged – and this attracts people who are far from having patients’ best interests at heart.

Not only does the ‘Right to Try’ legislation potentially allow more patients to be misled by these clinics, but it also undermines the authority of the regulatory bodies, and makes the rules regarding stem cell research confusing for legitimate scientists and clinicians. The importance of this can’t be overstated. Strong, clear regulation is the cornerstone of effective scientist research – and without it, vulnerable patients could end up spending hundreds of thousands on completely meaningless procedures.

Second Opinion

"Stem cell treatment for premature babies shown to be safe"

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WideCells CSO Peter Hollands examines new advances in the treatment of broncopulmonary displasia in premature babies – and the nascent stem cell source that’s behind it: An intriguing first step here towards using amniotic stem cells, sourced from the amniotic fluid or membrane which surrounds a foetus in the womb, to treat bronchopulmonary displasia (BPD), a disease which affects prematurely born babies.

This is very early, first phase work – the aim here is to establish not that the treatment necessarily works, but that it does no harm.

The results indicate that the basic concept behind this treatment is safe, and that the worst thing that could happen in further trials is that nothing will happen. That’s good news for further development of stem cell BPD treatment, and should give greater confidence to researchers and the parents of trial participants moving forward.

From an academic standpoint, it’s also interesting because we still don’t actually know the mechanism by which this treatment works (or if it does, with any reliability). There is some precedent for the use of amniotic stem cells, however. My colleagues at the Calcutta School of Tropical Medicine have been using them on a trial basis to treat severe burns for some years now, with a significant amount of success.

As well as, hopefully, giving some insight into how amniotic stem cells work, this study should also help to build more evidence for their clinical value. They have the potential to form a huge field of study in their own right, particularly due to their interesting immunological properties, which could make them very useful for treating autoimmune diseases such as arthritis. It’s still a nascent area receiving active focus from relatively few researchers, but with results like those in this story, that may begin to change.

Second Opinion

"Stem cells to be transplanted into brains of Parkinson's patients in world-first trials"
(New Atlas)

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Stem cells have been posited as a cure for Parkinson’s for more than 20 years. A new study claims to have made a breakthrough in this area. Widecells CSO Peter Hollands examines the evidence: Parkinson’s disease has long been an attractive target for cell therapy researchers. This is partly because scientistsen have a good understanding of its causes. We know that it occurs because dopamine cells in the brain are not working correctly, and we know where exactly in the brain those cells are located.

Progress in this area has been slowed by unsuccessful trials, however, so it is great to see good news once again coming from this field. The stem cells used in this study are induced pluripotent stem cells (iPSCs), a type of cell which can make virtually any type of tissue - one reason why we at Widecells are currently in the process of developing a clinical grade bank for them in collaboration with Manchester Metropolitan University.

In theory, it should be possible for iPSCs to develop into the fully-functioning dopamine secreting cells which a Parkinson’s patient needs to recover. But the difficulty is getting the iPSCs into the correct part of the brain in the first place. The method most widely tested in the past was an intravenous graft, the injecting of stem cells into the blood stream. This has proved ineffective, however, due to the blood-brain barrier blocking the cells from reaching the brain.

The solution these researchers are positing is the use of a gadget which involves cutting open a patient’s head to deliver the cells very precisely to a chosen point. Combined with the targeting enabled by CT scans, the prognosis for this treatment is really quite good – the main risks for patients taking part in this study will be the standard ones associated with undergoing open surgery, such as bleeding and infection.

But for those with terminal Parkinson’s, it will be a clear case of benefit outweighing risk – and it could mean that we have finally reached the point of a workable treatment for this horrendous disease.

Second Opinion

"Stem cells derived from dental pulp can cure deafness"
(News Medical)

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WideCells CSO Professor Peter Hollands on why we should be storing dental pulp and not throwing it away: This article is something of a tough read, due to a poor translation. But extracting the core findings, it seems there has been some very interesting work done with stem cells from dental pulp – still a rarely used source of stem cells, but one with significant potential.

They tend to be used for dental treatments, but since the cells are mesenchymal - meaning they can form a wide variety of nerves, muscle, tendons and bones within the body, not just teeth - there’s little reason why they shouldn’t be used elsewhere. This study is strong evidence of that, showing positive results for a clinical trial which uses dental pulp cells to treat deafness.

Considering the developmental embryology of dental pulp cells – ie, where they came from – they should in theory be particularly effective at making bone and nerves, both of which are key for treating hearing, which relies on small bones in the middle ear and sensory nerve pathways in the inner ear.

With their apparent effectiveness and flexibility, you might reasonably ask why dental pulp cells aren’t yet used more widely. The answer lies in the yields – a single tooth yields only a small number of stem cells. However, exfoliated or extracted teeth are currently generally discarded as medical waste, when they could be a rich source of stem cells if a routine process of collection and cryogenic storage was followed. In fact, I wrote a paper that covered this very topic among others recently.

This trial is more evidence of the efficacy and value of dental pulp stem cells as a resource, and demonstrates that it’s critical that we start ensuring that they’re stored and used, not wasted.

Second Opinion

"British scientists create artificial embryo from stem cells"
(Irish News)

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WideCells CSO Professor Peter Hollands examines the possibilities created by artificial embryos:

Louise Brown, the first ever test tube baby, turned 40 a few days ago – so it feels like an appropriate moment for news of advances in embryology to arrive.

The crux of this report is that researchers have been able to create and grow an artificial mouse embryo from scratch using stem cells, allowing us to study some interesting aspects of embryonic development that we may not have seen before. It’s an excellent piece of research (published in Nature, always a robust endorsement in itself), and has some interesting potential applications - but before getting too excited, it’s worth bearing in mind that this is purely experimental. Clinical use for this type of technology remains a long way off.

There is some talk in the article of the potential of moving from mice embryos to human embryos, and the possibility that this would allow researchers to perform experiments beyond the current legal 14-day age limit for human embryo experiments. No-one knows if this would be the case – and besides, the journey from mouse to man is a long one. There are no guarantees that we will be generating human embryos using this type of technology any time soon.

More interesting is the potential for the learnings from mice to help us understand the early developmental stages of humans better. A deeper understanding of these would eventually be extremely useful for clinicians working to prevent early miscarriages, and these are encouraging steps towards that.

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"Stem cell treatment for horses gets the green light"
(Vet Times)

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Following EMA approval, WideCells CSO Professor Peter Hollands reviews the use of stem cells in treating equine lameness: It’s no surprise that stem cells are now being used as a treatment for racehorses. These animals can be so valuable that their medical care is often better than that of many humans.

We’ve seen veterinary treatments expand enormously in sophistication over the past few years, with advanced techniques such as CT scans and orthopedic surgery now applied routinely. Approval by the EMA of stem cell treatment for equine lameness is just the latest advance.

The technique this article discusses shares a lot of similarities with the procedure that would be implemented for treating a human - when it comes to mammals, the principles are all broadly the same – featuring a single injection of donor stem cells directly into the joint.

The bone marrow cells used for this procedure are known as mesenchymal stem cells. They are able to produce more than one type of specialised cell. In this case, the mesenchymal stem cells have been specially treated in a lab beforehand to encourage them to produce only the desired cartilage cells once injected.

Interestingly, this is something of a reversal of the usual process of testing treatments on animals first. The efficacy of this procedure has already been demonstrated on humans (although the principles of mesenchymal stem cell transplant were first worked out in mice).

It’s also yet another sign of the gradual evolution from pharmaceuticals to cell-based therapy as the medical community’s predominant treatment method – animals included.

Second Opinion

"Routine DNA testing will save the NHS money and benefit patients"
(The Guardian)

What do our experts say?

Widecells CSO Peter Hollands gives his view on the news the British national health service will being using genomic medicine to establish the most effective treatments and reduce adverse drug reactions:

Fantastic news that the UK is to be the first country in the world to offer this remarkable DNA testing technology on the health service.

To understand why this is such a big deal, it’s useful to know how we treat patients at the moment. Our current system uses something of a ‘machine gun’ approach – patients with the same disease or problem tend to all receive mostly identical treatment. Some might respond well to the treatment, others not so well, and some people may respond very badly indeed. What DNA testing allows us to do is to avoid the latter two outcomes and to better tailor treatments to individual patients’ genomes — a technique known as ‘precision medicine’.

It’s not hyperbole to say that this is the next big step forward in the practise of clinical medicine. It will affect the treatment of all major diseases – including the two biggest killers, heart disease and cancer — and there’s no doubt that it will make treatment across the board significantly more efficient.

The bottom line here is that we can expect patients suffering from these diseases and others to recover more quickly and with fewer complications.

This is a clever and eminently practical step forward for the NHS. The quicker and more reliably patients recover, the faster they are out of hospital, and the lower the cost of treating them.

The health service can often find itself firefighting, but here we can see it taking a truly forward-thinking approach. Excellent news indeed.

Second Opinion

"Embryonic stem cells to treat heart failure? Nice idea — but we don't have the resources of stem cells"
(Independent Online)

What do our experts say?

WideCells CSO Professor Peter Hollands responds to a new report claiming stem cell therapy can be used to treat heart failure:

Back in the early '80s, it was a dream of many scientists to have frozen embryonic stem cells available on-tap as a resource for treating patients. It never happened. But the researchers behind this particular study seem to be resurrecting the idea.

Their motivation is a potential therapy they have developed for treating heart failure with embryonic stem cells. But the issues with creating a resource of this particularly scarce type of cell remains as complex as it was 30 years ago. Embryonic stem cells are simply much less plentiful than other types, and demand would rapidly outstrip supply for any routine treatment which relied upon them. Even if you employed every embryonic cell available in the world today, they would only be sufficient to treat a few hundred patients at most.

This is because the starting point for embryonic stem cells is the human embryo itself – not generally easy to come by for research purposes. The only current source of embryonic stem cells are IVF clinics, where embryos no longer required by patients are sometimes donated for research. But, even with tens of thousands of patients now undergoing IVF, these donations are still relatively rare. What’s more, once one of the elusive embryos has been acquired, there are no guarantees that stem cells can be successfully created from it.

There is a sliver of hope that this idea could be more practical if it incorporated a mix of stem cells, rather than an exclusive reliance on human embryos. But, for the moment, it’s a piece of research which is academically interesting, but unlikely to be clinically significant.

Second Opinion

"Stem cell donation is painless — the Will Smith film Seven Pounds is negatively influencing the public"
(Daily Mail)

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Widecells CSO Professor Peter Hollands reviews a report that nearly two-thirds of Britons would not donate stem cells because of a misrepresentation of stem cell donation in Will Smith's film Seven Pounds:

This is a shocking article – and easily the most important story that I’ve ever reviewed on Second Opinion. Unlike most other stem cell news, this isn’t theoretical, it’s something that’s happening right now – and it’s having a major, negative impact on the people who are lying in hospital waiting for a donation.

It can’t be emphasised enough how easy it is to donate stem cells today. Potential donors don’t even need a blood test beforehand, simply to self-administer a cheek swab with a kit that arrives in the post. For those eligible to donate, the process is similar to giving blood, and just as safe, easy, and painless.

What’s more, donating stem cells is incredibly important. Every day, thousands of patients are waiting for stem cell transplants – that means it’s critical that the stem cell community gets across the message that donation is easy to do, it’s not dangerous, and it will quite literally save lives.

We’ve got a very weird situation here, where we’ve got people scared off becoming donors – by a film, of all things - but we’ve actually got a very convenient and painless system for enabling them to do so.

It’s discouraging, especially when you consider the reality of what the need for stem cell donation means - thousands of children and adults lying in hospital beds, potentially not ever finding a matching donor. Registering to undergo this simple, painless process should be a no-brainer for everyone.

Second Opinion

"Cord blood transplant treatment holds promise for blood cancer patients"
(Straits Times)

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Widecells CSO Professor Peter Hollands calls for caution following the results of a cord blood transplant in clinical trial for treating blood cancer:

What we have here is a new method of what’s called ‘cell expansion’, a process of stimulating of stem cells to divide and therefore increase their overall number. It’s a critical element of the process of treating adult patients with cord blood, since a single extraction provides only enough stem cells to treat a child (the bigger the patient’s body, the more stem cells are required to treat them).

It’s mind-boggling the number of experiments and clinical trials focusing on cell expansion currently. The trial this article looks at seems to have been ongoing for some time, and is using technology that has been knocking around for at least 10 years now. What is interesting is that they now have a patient who has benefitted enormously, which helps to demonstrate that we’re now approaching a point where we can expand cells reliably, something which has eluded those in the stem cell field for a number of years now.

That said, it’s still early days in many respects. The usefulness of stem cell expansion still remains to be proved – this particular trial is clearly still at the Phase 1 ‘Safety and Efficacy’ stage, and a Phase 3 clinical trial generally takes between five and ten years. In a decade or so we should have the answer to the question of whether expansion is useful clinically. If it isn't, we might have to abandon the concept of expansion entirely.

The ongoing results of the trial in this article are promising. So I do think there’s reason to be cautiously positive about the future of this method.

Second Opinion

"Delivering stem cells to a damaged heart is unlikely to be non-invasive "
(Science Blog)

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*Widecells CSO Professor Peter Hollands casts a critical eye over a new and potentially non-invasive method of treating the heart with stem cells: *

It sometimes feels as if every man and his dog are working on stem cell treatments for the heart at the moment (including me!). It’s astonishing how many new therapies are being developed, most of which are focusing on how to repair the heart following a heart attack.

Heart attacks are classically caused by blockages to the blood vessels that supply the heart. The tissue around those blood vessels then dies, turning from muscle into scar tissue. Healing that scar tissue is the key goal of many of the stem cell therapies in development.

Most of these aim to work by placing the cells in situ on the heart, in order that they can release chemical compounds to stimulate the patient’s natural repair mechanisms.

The trick is getting the stem cells in place. The researchers in this article are aiming to place a ‘patch’ of stem cells on the heart, and a key proposed benefit is that this is relatively non-invasive. I don’t quite understand that, as I’m not sure how you get the patch onto the heart without being invasive. It is possible that they’re using an endoscope – pretty invasive in of itself — but otherwise to reach the heart, you have to split the breastbone, which is self-evidently invasive.

There is also a question hanging over how the reservoir of cells in the patch can be replenished. It’s not clear if this would be via an external port installed on the patient, something that would raise the possibility of infection if the patient wasn’t kept within an ICU.

However, it’s another interesting method to add to the list — the competition in this space is fierce, and I’m very curious to see what proves the most viable.

Second Opinion

"We haven't been studying gene editing for long enough to truly understand the risks"

What do our experts say?

WideCells CSO Professor Peter Hollands on a report suggesting gene editing increases the risk of cancer:

When you start fiddling around with DNA – and, by association, genes – you don’t really know what the long term outcome will be. There’s the potential for a patient who had appeared fully recovered to then develop hideous issues 20 years later. We simply haven’t been collecting data on gene editing for long enough yet to know.

This is common knowledge among those in the field, which is why I’m surprised to see this article raising the issue of potential gene editing complications (such as cancer) so strenuously. Any patient undergoing this still highly experimental treatment would need to understand the risks, and as is often the case, those who choose to undergo it will be those who consider the risk/benefit analysis to be favourable – i.e. the outlook without undergoing the treatment is sufficiently poor that it is worthwhile to take the risk.

The scientists in this report are being ultra cautious - ultimately all of these experimental treatments have risks associated with them, and this is only the first generation of gene editing. It’s comparable to the early days of penicillin and antibiotics. We need the technology to be more widely adopted before it can improve. Once that happens, things can change incredibly rapidly. Ten years from now, the technology this article focuses on could well be obsolete. By then we’ll have hopefully moved onto second and third generation technology.

The potential of gene editing is tremendous. Testing it is a must. There will always be risks with new technology, but for patients with poor prognoses, those risks could well be worth taking.

Second Opinion

"Acid attack victim may regain sight with stem cell treatment"
(Evening Standard )

What do our experts say?

WideCells CSO Professor Peter Hollands reports on work being conducted to restore eyesight using stem cells:

An interesting case here, with an acid attack victim blinded in one eye undergoing stem cell therapy 24 years after the fact. If they can restore his vision, as far as I’m aware it would be a world first.

This isn’t the only work being conducted to restore eyesight with stem cells (a clinical trial is currently ongoing using embryonic stem cells, with the aim of repairing the retina, for one), but this particular case appears to be focusing on repairing the conjunctiva. This is the mucous membrane at the front of the eye, which, needless to say, would have been badly damaged by this type of assault.

The eye has a distinct advantage for this type of treatment, because it’s what we call an immunologically privileged site - meaning any cells can be transferred in there and the immune system won’t reject them. But something to bear in mind about this trial is the length of time between the injury being sustained and the treatment. Attempting to treat an eye damaged by acid with stem cells immediately – or even a few weeks later – would be unlikely to work, since the eye would be so severely inflamed that it would be totally non-receptive to new cells.

However to coin a phrase, time is a great healer. After 24 years, the inflammation will have disappeared, and the micro-environment into which the cells will be transplanted should be much more conducive to their survival. But it is worth noting that immediate inflammation is likely to be a limiting factor on how quickly this treatment method can be used in future, should it be proved viable.

Second Opinion

"Tiny baby undergoes stem cell transplant while still in the womb — a remarkable achievement"
(The Mercury News)

What do our experts say?

A tiny patient — still inside her mother’s womb — has been treated with a stem cell transplant, derived from her mother’s bone marrow, at UC San Francisco. WideCells CSO Professor Peter Hollands on a tremendous achievement in stem cell treatment:

A huge achievement here, as a child successfully receives a stem cell transplant for alpha thalassemia while still in the womb – a genuine first. For years the idea of treating babies in utero has been discussed, but the scientists and clinicians in this report are the first to have actually cracked it.

There are a variety of factors that have prevented in utero treatment in the past, primarily inadequate scanning technology and the great difficulty in injecting directly into an unborn baby. In the case of the former, technological advances now mean we can get sufficiently detailed 3D pictures of the baby – but the latter is very much a test of the clinician’s technical skill in injecting into the umbilical cord vein through the mother’s womb. It’s a challenging procedure and it’s impressive that someone has managed to pull it off.

The uses for this type of treatment extend far beyond alpha thalassemia. Anything you can diagnose in utero could be potentially treated by this method – and it’s possible that we could also treat foetuses with parts which have not properly developed. This is in part because of a significant boon of in utero treatment – the foetus’s as-yet undeveloped immune system. This means that it does not reject donor stem cells, and that there is little to no risk of Graft-versus-Host Disease – a disorder which can be a major issue for stem cell transplants in children and adults.

In other words, if we can treat babies before they are born, all the better – and while the technical skill necessary for in utero treatment means that it remains a risky procedure, we now have incontrovertible evidence that it is possible. Very good news indeed.

Second Opinion

"We're still a long way from a 'blood machine' — but progress is being made"

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Blood on tap? Widecells CSO Professor Peter Hollands examines a breakthrough that could eventually revolutionise transfusions:

Back in the 1990s, I was part of a team working to develop artificial bone marrow – not only for its own sake, but to eventually create what we called a ‘blood machine’, a device which could theoretically supply an endless number of new red blood cells for clinical use. It would have eliminated the problems of transfusion units running out of cells, eliminated reliance on donors, and provided clinicians with blood cells quite literally on tap.

The researchers in today’s report are working towards something similar – we too undertook the first steps by growing artificial bone marrow using stem cells. Ours would grow reasonably well for just a brief period before, invariably, beginning to die. We never fully understood why.

It’s heartening to see that the scientists in this report seem to be faring better, thanks in part to their crafting of a more welcoming microenvironment for the crucial stem cells, as well as their use of today’s much more advanced bioreactor technology.

We’re still a way off the ‘blood machine’. The artificial marrow will need to survive for a month or so before producing beginning to produce blood cells, and still only lasts a few days at present. But we are getting closer, and that’s exciting news.

Successful production of healthy artificial marrow wouldn’t only be a boon for blood transfusions, but could also provide a valuable testbed for new drugs, enabling pharmaceutical companies to accurately test thousands quickly, and without the need for human subjects.

So, imperfect technology, but with great promise – and one of the most positive reports I’ve seen in this field for some time.

Second Opinion

"Spinal injury repair using stem cells? Latest research is a step in the right direction "
(The Scientist)

What do our experts say?

Widecells CSO Peter Hollands looks at the latest progress towards the ‘holy grail’ of clinical research:

Spinal injury repair – the cure of paralysis, essentially – is in many ways the holy grail of clinical research. It’s something that has been talked about for many years with little progress, and stem cell research in particular has been hamstrung by the fact that damaged spinal cords tend to be a poor quality environment for cells to survive. At least, they don't survive long enough to have a positive effect. With that in mind, it’s always good to see a story with news of some progress in this area. This report focuses on a study using participants with long term spinal injuries and the associated paralysis. Each has been injected with stem cells extracted from a donated spinal cord, and the results are intriguing.

While no participant reported an improvement in overall quality of life, some did report a degree of increase in sensation. What’s more, there was some sign of neurological recovery in the patients’ spines, something we’d usually associate with repair of the lesion causing their paralysis.

While this might seem a long way from a paralysed patient standing up and walking around, from a research perspective it’s very encouraging. This was only a ‘phase 1’ clinical trial, concerned primarily with ensuring that the treatment undergoing testing doesn’t cause harm, rather than evaluating its ability to heal. Results of the magnitude seen here should hopefully help to lay the groundwork for an eventual clinical trial.

Encouraging work – and a very necessary step on the path to reaching genuinely effective treatment for spinal injuries.

Second Opinion

"'Reprogrammed' stem cells may be used to mend human hearts in 'intriguing' breakthrough"
(Scientific American)

What do our experts say?

This is a potentially revolutionary treatment for heart disease — but is there enough evidence for its effectiveness? Widecells CSO Peter Holland offers his view:

A unique breakthrough in heart disease treatment has been reported here. It involves the development of a thin ‘tissue’ of stem cells that can be laid directly on the surface of a patient’s heart.

This is significant for two reasons: firstly, it’s a new method of introducing stem cells into the patient’s body. And secondly, it’s a new route to potentially treating the heart with stem cells, something which we haven’t in the past been able to achieve.

It’s promising work on both counts. The ‘tissue’ method of stem cell application holds potential for placing stem cells in other areas - I can imagine perhaps growing nerve cells and grafting them into the nervous system, for example — but perhaps more importantly, it could act as strong evidence for the efficacy of stem cells in treating the heart.

Attempts have been made to treat myocardial infarction (heart attack) patients with bone marrow stem cells before, but without success. But in this study, the relatively nascent technology of induced pluripotent stem cells (iPSCs), has been used instead of bone marrow.

These are normal cells – mature skin cells, for example – which are treated with a special set of genes that are converted (or ‘induced’) to become stem cells. We know that these can make heart muscle cells, but for clinical use they are as yet unproven.

The only way to change this is to run clinical trials. For this, scientists are dependent on the participation of end-stage heart disease patients for whom the options are running out. That slows things down for obvious reasons. But signs are otherwise positive for this technology. Intriguing work.

Second Opinion

"Dilanubicel is great news for leukaemia patients"
(Geek Wire)

What do our experts say?

Widecells Group CSO Peter Hollands examines claims that a new drug dramatically increases the effectiveness of stem cell treatments for leukaemia:

This is a case of the facts genuinely living up to the headlines. We have the molecule known as the ‘notchligand’ to thank for these remarkable results. Of the leukaemia patients who received a combination of a stem cell transplant and dilanubicel, a new drug containing notchligand molecules, 86% are now cancer-free.

The secret to the success of dilanubicel lies in its ability to exploit the notchligand to stimulate stem cell expansion, the process by which a small sample of stem cells are extrapolated to the numbers required for effective treatment. These numbers vary from patient to patient based on body weight, and are of increasing importance due to the rising use of umbilical cord blood as the first-choice source of stem cells.

Cord blood has a terrific advantage in that its cells do not carry a risk of triggering Graft-versus-Host Disease when transplanted into patients (in contrast to other sources, such as bone marrow) but a downside in that a sample of cord blood yields only a relatively small quantity of stem cells.

This means that clinicians are more dependent on a rapid process of cell expansion for successful treatment, in order that what’s known as “engraftment” can take place quickly. Engraftment is the process by which the transplanted stem cells begin making new blood cells, and the point when the patient’s healing begins. The faster this process can take place, the better the prognosis.

The bottom line is that there is now good evidence that the use of dilanubicel increases the long-term survival rate of patients. This is good news for stem cell scientists and even better news for current and future sufferers of leukaemia.

Second Opinion

"The science behind the human-chicken embryo is truly groundbreaking"
(Tech Times)

What do our experts say?

Sensationalism or a significant discovery? Widecells CSO Professor Peter Hollands takes a look at an experiment to hybridise human and chicken cells:

This report on the creation of a hybrid embryo of human and chicken cells is significant. But it is, arguably, sadly trivialised by some sensationalist reporting.

It focuses on the suggestion that researchers behind the study sidestepped laws regarding experimentation with human embryos over the age of 14 days. But the point – that we now have a path to a much better understanding of a number of areas of human development that remain a mystery — has been somewhat lost.

Putting aside the 14-day age limit on human embryo experimentation (irrelevant in any case, since human embryos do not survive outside a mother for much longer), there is excellent work here in better understanding the role and mechanism of what are known as “collector cells”.

Collector cells are the creators of stem cells: the cells which power organ generation, and the cells at fault when birth defects occur.

Our current understanding of them is poor. But if we can begin to learn more about them, the potential applications are tremendous. We could start to understand how organ regeneration works, and what causes a variety of birth defects. Areas it could shed light on range from miscarriage to Down’s Syndrome. Not to mention the potential benefits in treating other stem cell-based diseases, cancer included.

This is extremely important work. The study’s original publication in Nature, the pre-eminent scientific journal, is the proof. You don’t get published in Nature unless your work is genuinely groundbreaking — and this certainly qualifies.

Second Opinion

"Amateur 'biohackers' pose a risk to us all"
(New York Times)

What do our experts say?

Widecells Group CSO Peter Hollands takes a look at the burgeoning amateur ‘biohacking’ field, where enthusiastic amateurs are experimenting with gene editing in garages:

This is a new one for me — a report from the New York Times about amateur ‘biohackers’, who are purchasing gene editing equipment and precursors online, in order to carry out experiments in makeshift laboratories in garages.

Some of their work seems fairly benign. For example, the former biohacker now working for Stanford University to build a library of frozen genes for experimentation could actually be creating a useful research resource for professional scientists. But with good reason, the Times article focuses on raising the alarm regarding the potential damage these hobbyists could do.

Not only do some appear to be experimenting on themselves, something someone who understood the risks (a molecular biologist, for one) would never do. But, there is also the potential for someone with the inclination to potentially create a new, resistant strain of an eradicated disease, such as smallpox.

I hardly need to add that the danger of this would be significant, and the key takeaway from this piece is that regulators need to act quickly to stamp this activity out. After all, we’ve been here before – a nascent field, enthusiastic amateurs, an inherent risk to the public at large – with fears in the 1990s over hobbyists meddling with human embryos, at the dawn of proper stem cell research. Much earlier, we had home alcohol stills creating potentially lethal moonshine, an activity to which the bar to entry was much lower.

You could still do both, in theory. But almost no one does, because the regulators stepped in and took control. That’s what needs to happen here, to limit the risk both to the biohackers themselves and - more importantly - to the rest of us.

Second Opinion

"Robot-made 'organoids' have huge potential"

What do our experts say?

WideCells CSO Peter Hollands examines the rise of the robots in stem cell ‘organoid’ research:

Scientific research is a test of endurance. Thirty years of work might result in just a single ‘eureka!’ moment – and that’s if you’re lucky. It’s one reason why automation is rife in science, since there are often repetitive tasks which need to be accomplished continuously over a long period of time. It’s infinitely preferable for a tireless robot to perform these, especially since they don’t tend to make mistakes (unlike human researchers, who sometimes make costly ones).

That’s why new innovations in this area are always a good thing. In this instance we’ve got robots that will allow us to create organoids – micro versions of human organs, created from human stem cells and ideal for in vitro drug testing – more quickly and more efficiently.

Organoids have a lot of potential for enabling us to test the effectiveness of treatments before administering them to patients, and to test new drugs without often-unreliable animal-based experiments. In the future, they could also help enable the usage of ‘personalised drugs’ – custom pharmaceuticals tailored directly to individual patients.

But organoid technology is not yet mature enough for these clinical uses. The labour-saving robots in this article should help to speed up research by removing the need for human supervision of the most tedious elements – and will hopefully help us to move towards helping patients more quickly.

Second Opinion

"Alzheimer’s "gene fix" proves promising"
(San Francisco CBS)

What do our experts say?

Widecells Group CSO Peter Hollands responds to a new report claiming to be a potential breakthrough for the treatment of Alzheimer’s Disease:

Progress in treating Alzheimer’s remains slow, and the past decade has seen a number of seemingly promising treatments prove disappointing at the clinical trial stage. But a new study seems to have revealed an intriguing path forward – with stem cells providing the key.

Neurodegenerative diseases such as Alzheimer’s primarily affect the body and brain through nerve damage triggered by toxic accumulations of proteins – but exactly which proteins constitute the greatest risk factors is not clear. The authors of this study claim to have narrowed down the search to ApoE4, a gene which produces proteins which constitute a direct and malignant cause of toxic protein build-up. They then conducted a successful test of compounds designed to change the structure of the harmful gene, a step which could be significant in Alzheimer’s treatment research.

Their results are encouraging – not least because they eschewed research on mice in favour of employing induced pluripotent stem cells (iPSCs). As chief researcher Dr Huang points out in the article, mice models can be useful but are frequently unreliable predictors of how a treatment will work on humans. Over-reliance on them is arguably partly responsible for many of the disappointing clinical trial results we’ve seen for treatments for neurodegenerative diseases.

By contrast, iPSCs are real human stem cells – and consequently allow researchers not only to have a live, working model of exactly how a pathogen or disease functions in the body, but also a live human testbed for treatments. It’s another example of the flexibility of stem cells, and more evidence for just how crucial they will be as we transition from primarily pharmaceutical treatments to a greater focus on gene and cell therapy.

Second Opinion

"Discovery of a "new organ" is likely to be an error"
(New Scientist)

What do our experts say?

Centuries after we first began studying anatomy, is it still possible to discover new organs? Widecells CSO Peter Hollands examines the evidence.

On the face of it, this account of a newly discovered human organ looks like a major breakthrough. The reality, however, is unfortunately rather less exciting. Known as the lymphoreticular system, the ‘network of fluid filled channels’ described in the article is in fact something scientists have been familiar with for quite some time.

The study the article is concerned with has provided some new microscopic evidence of how the system works that we haven’t been privy to before. But the idea that it might influence cancer treatment is likely to be erroneous.

Technically, samples from the fluid in the lymphatic system can be used as a method of cancer diagnosis, since the malignant cells responsible for forming tumours tend to use it to spread around the body. The suggestion here is that the new evidence provided by this study might help us to more easily sample this fluid, and therefore diagnose cancer earlier.

The problem with this is that by the time the malignant cells are present in the lymphatic system, the tumour is no longer at an early stage – it’s already spreading. It’s unlikely that diagnosis via lymphatic fluid will be any more useful than other, more convenient methods available at this point.

There is the potential for the study’s findings to help us better diagnose liver disease and oedema, both also associated with the lymphatic system, but this is very much an unknown at this point.

A quite interesting discovery, then, but not one likely to have a major impact on clinical treatment – and certainly not an entirely new organ!

Second Opinion

"Stem cells cure alcoholism in rats "
(New Atlas)

What do our experts say?

Widecells Group CSO Peter Hollands responds to claims that rats have been cured of alcohol addiction through stem cell injections:

This new study claims to be a breakthrough in the treatment of addiction. Using experiments on rats selectively bred to be alcoholics, scientists have demonstrated that stem cell injections appear to almost entirely terminate cravings for booze.

The treatment itself was simple. The rats, who up until the point of treatment were choosing to ingest the human equivalent of a bottle of vodka per day, almost entirely lost interest in alcohol after an injection of human mesenchymal stem cells. Within 48 hours they had voluntarily dropped their intake by over 90 percent, overwhelmingly selecting water over alcohol.

It appears to have worked by exploiting the mesenchymal stem cells’ anti-inflammatory effects. They proved effective in treating the chronic, whole-body inflammation that is both a chief by-product of alcohol abuse, and a chief cause - appearing as a result of extreme alcohol intake then acting as a catalyst for cravings for more alcohol. Good news for alcoholic rats, but is it likely that this effect will transfer to human patients? The findings are certainly likely to be relevant to our own species, since rats are fellow mammals. But the cause of alcoholism in humans is not confined to biological cravings. If this treatment is transferrable, it won’t tackle the social and psychiatric issues which are often significant factors.

But even with that proviso, this discovery could still be tremendously useful to the treatment of alcoholism, and could even become a routine part of treatment courses. It also constitutes another piece of convincing evidence that we are headed towards a future where cell therapy will replace chemical pharmaceuticals almost entirely.

Second Opinion

"Can stem cells get to the root of mental illness?"
(Scientific American)

What do our experts say?

Widecells CSO Peter Hollands gives his view on new work aimed at using stem cells to create personalised drugs for treatment of mental illnesses:

This article is based on research into the use of stem cells to identify the drugs which individual mental health patients will best respond to.

In this process, researchers use induced pluripotent stem cells (iPSCs), or stem cells that have been created from mature cells collected from the patient. Importantly, following their transformation into stem cells, iPSCs retain all the characteristics of the patient’s cells as a whole – so you’ve instantly got an in vitro model on which you can begin testing drugs for their effectiveness.

This has clear advantages – in particular the article discusses the use of lithium, which remains a common treatment but has horrible side effects. If this iPSC-based method could be used to safely screen alternative drugs, a less toxic alternative might be found for a patient.

Studies of this type represent the initial steps towards the idea of ‘personalised medicine’, i.e. the tweaking of individual drugs for a specific patient’s needs, with maximum efficiacy and minimal side effects. This is still at the conceptual stage, however, studies such as this one bring us closer to at least being able to select the most effective off-the-shelf drug for an individual patient.

Unfortunately, even this is still some way off. The article mentions an estimate of a decade or two until this technique is used clinically. I think that’s reasonable. The main stumbling block currently is that there are only a few labs in the world currently capable of producing iPSCs well.

Until the technology for their production is further refined, we can’t expect to see this type of work being done in the average district hospital.

Second Opinion

"Baa-d idea? Sheep could grow donor organs for humans"
(The Mirror)

What do our experts say?

Sheep as human organ incubators – clinically credible or woolly thinking? Widecells Group CSO Peter Hollands gives his view on a recent report in The Mirror newspaper.

Despite the Mirror’s hyperbole, this is far from a "shock breakthrough" – we’ve covered some other recent work in this regard on Second Opinion recently, and the idea itself has been around for at least 20 years.

The process they’ve used in this instance calls for sheep embryos to be injected with human cells, following undergoing what is referred to as "knockout" – the process of preventing specific genes from functioning.

In this case, the genes that code for the placenta have been disabled. The idea is then that the injected human stem cells will create a human-sheep chimera which produces pancreas cells that may be extracted for transplant into a human.

This is interesting experimental work. But, clinically, I can’t see it being relevant any time soon. The main problem is that this approach is overwhelmingly complicated compared to other stem cell-based treatments that we could perform much more easily.

The most obvious alternative would be to produce and use induced pluripotent stem cells (iPSCs). These flexible cells can create many different kinds of tissue, and can be produced in a lab from mature cells extracted from a patient.

Another alternative would be mesenchymal stem cells, which can be drawn from a patient’s tooth pulp among other areas, and which have been shown to be able to rebuild the pancreas. No animals required, no embryos required – a much simpler process, and much closer to being clinically practical.

Second Opinion

"Injecting a penis with stem cells? There's no science behind this whatsoever "

What do our experts say?

Widecells Group CSO Peter Hollands ponders the efforts of a self-styled “science experiment” to cosmetically enhance himself with stem cells:

This article takes a look at a particularly silly pseudo-cosmetic treatment, featuring a ‘human science experiment’ injecting himself with stem cells with the aim of enlarging his penis. He seems to think it worked – and while I’m very happy for him if that’s the case, the long and the short of it is that there’s really no science behind this whatsoever.

The beneficial effects of injecting stem cells into the penis are probably non-existent, as the body likely recognised the cells as foreign and destroyed them before anything else could happen. The dangers, particularly of infection and bleeding, are quite real however.

Injecting stem cells is an invasive procedure, and certainly not something I’d recommend to anyone, particularly as this sounds like it was a ‘do it yourself’ in a non-clinical environment without a medical professional.

There are some potential legitimate uses for stem cells in male genital treatment, however. Prostate cancer is mentioned briefly in the article, and that’s something that we at Wide Cells have interest in. Treatment of the disease currently tends to cause erectile dysfunction, and there is some evidence that cell therapy could help to reverse this.

There are also potential cosmetic applications for stem cells too, although penis enlargement isn’t on the list. Research has been done into the potential for cell therapy for anti-ageing. It’s fairly controversial, but has its basis in the fact that the ageing process is based on the ageing of our stem cells.

With a constant replenishment and replacement of a patient’s old stem cells with new ones, the theory is that you may be able to battle the effects of ageing. This type of treatment is a long way off, but remains much likelier than the kind of enhancement this article discusses.

Second Opinion

"Can stem cells really give us a vaccine for cancer?"
(New Atlas)

What do our experts say?

Widecells Group CSO Peter Hollands discusses reports of a "breakthrough" by Stanford University which suggests stem cells could be used to form a cancer vaccine.

The article reports that a combination of induced pluripotent stem cells (iPSCs) and an immune-stimulating drug have been shown to effectively destroy tumours in animal test subjects, namely mice.

It’s nice to see iPSCs in the news once again, but for the moment I think we can file this under "good news for mice".

It seems that the scientists conducting the experiment have used inactivated iPSCs alongside an "adjuvant" – an immune system-affecting drug – in order to stimulate the immune system to destroy the tumour.

The antigen expressions found on the surface of the iPSC cells sometimes correspond with the molecules found on a cancer cell, even though iPSCs don’t make tumours.

This has enabled the scientists to "train" the immune system to attack regularly injected stem cells – training which they then applied to the superficially similar cancer cells that the mice were later injected with.

Whilst this is an interesting experiment, it isn’t a solution (at least,not yet) or indeed a "vaccine" as reported.

If this test were replicated on humans it could produce a completely different set of results. For the moment we’re not sure whether this will prove useful or not.

However, it is a promising sign to see iPSCs appear in more reports as they have a huge potential, so it’s certainly a step in the right direction.

It would require an enormous clinical trial to find out whether this approach is effective, though.

It’s very likely there will be cellular therapy against cancer one day and iPSCs could be the basis for it.

This represents one example of what it might look like in the future.

Second Opinion

"'Stem cell plastic chips' may not be as forward-thinking as they sound"
(Daily Mail)

What do our experts say?

Widecells CSO Peter Hollands gives us his views on the potential for having our personal stem cells stored on a plastic chip, as reported by the Daily Mail:

The concept here revolves around the potential for induced Pluripotent Stem Cells (iPSCs) to be taken from a patient and stored on a plastic ‘chip’, where they may act as a way of screening pharmaceuticals for the patient.

We all interact with drugs differently. This method means we could potentially eliminate the sometimes painful (and often costly) trial-and-error processes that patients often have to endure for serious diseases such as cancer. Instead it would enable us to quickly highlight the best drug for an individual.

The chip itself is a form of mini bio-reactor that cells are put onto.

This concept isn’t really a massive breakthrough, the basic idea has been around for 15 or 20 years now – i.e. you put cells on the chip, they grow, and you can look at them and study them.

The new aspect here is the drug testing. But I would guess that these chips are not at all close to being used clinically for this purpose.

In some ways this technology is a bit of a sideways step, too. Long-term, we’ll most likely be moving away from drugs towards cellular therapy, where the cells themselves become the drugs.

This technology calls for the cells to be used as a testing ground for the drugs, which is interesting, but ultimately not quite as forward-thinking as pure cellular therapy research.

That said, if this work eventually helps us to use fewer animals in early pharmaceutical testing, that would be a good thing – and the data gathered would also much be better quality, as the drugs are reacting with real human cells rather than mice cells.

Second Opinion

"'Exciting' reports of first lung stem cell transplant trial in China"
(Eureka Alert)

What do our experts say?

WideCells' CSO Professor Peter Hollands gives his opinion on reports that a team from Tongji University, China have successfully regenerated a patient's damaged lungs using a stem cell transplant:

Some brilliant results here from a clinical trial into the efficacy of using stem cells to treat chronic lung disease.

A major cause of morbidity globally, lung diseases are also on the rise as pollution worsens around the world. So it’s always exciting to see positive progress in treating these.

This particular trial focused on the use of stem cells P64 and KRT5, two lung cells well known to researchers. First identified back in 2013, they have the ability to regenerate some of the structures of the lung, including the ‘terminal ends’ where oxygen diffusion takes place.

These are of particular importance for treating human lung disease, and research has been going on into how these can be regenerated clinically for some time. It now appears to be coming to fruition.

The process they’ve followed here is fairly standard in many ways – a brush bronchoscopy, essentially a direct tube into the lungs, to acquire a small sample of stem cells which are then ‘amplified’ by treatment in a laboratory to increase their number.

What’s great to see however is that this is an autologous procedure – i.e. it uses the patient’s own stem cells, not those of a donor.

Far more convenient and more reliable than finding a matching donor and extracting their cells, and without the associated risk to the patient of Graft-versus-Host-Disease, with autologous treatments the patient is literally carrying the cure in their own body.

The results from this study appear to show that this technique is working – Dr Zuo claims 80 total patients in a placebo controlled study, which is fantastic.

A very exciting piece of research.

Second Opinion

"Working kidney cells grown in mice is laudable — but we're a long way from a clinical application for humans"
(New Atlas)

What do our experts say?

WideCells Group CSO Peter Hollands reviews a report in New Atlas that functional kidney tissue has been developed from stem cells for the first time:

The new study in this article claims that working kidney cells have been generated and transplanted into mice for the first time.

This is interesting in itself - although experimental bioprinting has produced similar results in the past - but is also particularly of note for the researchers’ use of human pluripotent stem cells (PSCs) in achieving this. This highly adaptable form of stem cell that can in theory generate every type of human tissue. The organ regeneration seen in this experiment is a relatively new use of these versatile cells, however. However, the use of PSCs clinically remains a long way from viability.

A major barrier to use of PSCs in treating humans is the danger of Graft-versus-Host-Disease - likely eliminated in this experiment through the use of mice without immune systems.

If the experiment was performed on a human patient, however, there would be a significant risk of their body rejecting and destroying the transplanted kidney cells.

We are getting closer to using PSCs for treatment in some areas – particularly the eye, with clinical trials currently ongoing to test the safety of using PSCs to deal with diseases of the retina.

But the use of PSCs remains highly experimental, meaning that while this kidney regeneration work is interesting, there’s no real clinical basis to it yet.

Second Opinion

"Tasmanian devils with cancer treated using experimental stem cell therapy"
(Eureka Alert)

What do our experts say?

I’ll confess that this is a new one for me, writes WideCells Group CSO Peter Hollands.

I’ve certainly not heard of induced pluripotent stem cells (iPSCs) being used in the treatment of animals before.

It’s the iPSCs, rather than the Tasmanian devils, that are of most interest for our purposes.

These highly adaptable stem cells are created from mature adult cells, often drawn from the patient themselves rather than a donor, and consequently ensuring a perfect match during transplant (with no danger of Graft-versus-Host Disease).

They are not in general clinical use yet, but trials to demonstrate their potential are ongoing.

This experiment with Tasmanian devils is another test that helps to demonstrate the use and development of this technology.

The data from this experiment should provide valuable information to help us move towards the use of iPSCs in humans.

This particular trial focuses on treating a disease that I don’t think has an obvious equivalent in humans, a type of transmissible tumour.

However, the theory is the same as it would be in treatment of a human disease such as multiple sclerosis – the researchers are generating the Tasmanian devil iPSCs in order to create a model to study, understand and eventually learn how to treat the disease.

Just as the scientists who are undertaking this research hope to cure the animals’ tumours, the hope is that one day iPSCs will enable us to study and treat various cancers and other diseases in humans.

It’s very much in the future for now, but trials like this do help to bring us closer - even when they are conducted using animals.

Second Opinion

"Can a 'stem cell gun' really revolutionise treatment for burns victims?"

What do our experts say?

This is an interesting story, although I sense the writer might possibly be guilty of a bit of exaggeration, says WideCells Group CSO Peter Hollands.

The stem cell ‘gun’ is claimed to be capable of healing large areas of damaged skin - like those caused by a major burn — by spraying just a small amount of stem cells.

If it can live up to its maker’s claims, it’s an amazing breakthrough.

Currently, large second and third degree burns are generally dealt with via skin grafts, which effectively call for skin to be sliced off an unburned area of the patient’s body, then re-attached over the top of the burn.

This technique has been in use for at least fifty years and is hardly ideal, as it requires a doctor to cut open an already heavily injured patient – in the process creating a second wound which will then also have to be treated.

But the article claims that the new ‘gun’ requires only a postage stamp sized area of healthy skin to be removed from the patient, from which stem cells are then extracted and sprayed onto the afflicted area.

The spraying is interesting in and of itself – while aerosols are frequently used medically, I’ve not seen it in cell therapy before.

However, a question does hang over the stem cells’ effectiveness in such a badly damaged area.

If someone has just suffered a major burn, there are all sorts of chemical reactions going on under the skin – and it’s uncertain whether the stem cells could be relied upon to survive in this sort of environment.

It is, however, an interesting idea, and I’m interested to see how this develops over time.

Second Opinion

"Scientists hope to unlock mysteries of jaw development"
(Phys Org)

What do our experts say?

WideCells Group CSO Peter Hollands reviews findings by the USC Stem Cell laboratory of Gage Crump revealing how "key genes guide the development of the jaw".

While the human genome was first fully sequenced in 2003, the functions of the vast majority of genes within it remain a mystery.

This article covers a new study which reveals the roles of two key genes in the development of the jaw, using a new method which the scientists propose could be used for further genetics research.

The catch? The genes in this study aren’t from humans, but zebrafish. It goes without saying that zebrafish are biologically completely different from humans, their genes likely even more distant from ours than the oft-studied mouse’s (which is at least a fellow mammal).

Nonetheless this is interesting work from an academic point of view, and it has the potential to be massively significant in the future. The background information provided by this project might later be extrapolated to humans, in this case in terms of understanding how genes affect skeletal development.

It’s also useful that they’ve developed technology that can look at the gene functions of the fish – again, this should be a step towards us being able to do the same thing with humans. A human’s genome can now be sequenced cost-efficiently in about a week. If we can link this to a better categorisation and understanding of individual genes’ roles, it will be a quantum leap forward. The impact on treatment will be enormous.

That remains some way off however – for now this is an academically interesting piece of research, but one likely to only have clinical impact for humans in the very long term.

Second Opinion

"Scientists discover gene behind blood-forming stem cells in potential breakthrough for blood cancer treatment"
(Medical Net)

What do our experts say?

WideCells Group CSO Peter Hollands reviews new research by UCLA and the University of Iowa suggesting the discovery of a specific gene that gives rise to blood-forming stem cells.

This article covers a new study that reveals the function of the gene Pi4Ka.

It’s an exciting discovery - every new gene that we know the purpose of brings us closer to a comprehensive understanding of the still mostly mysterious human genome.

But from a clinical medicine perspective, it can open something of a can of worms.

The reason why lies in the function of Pi4Ka. We now know that it’s responsible for releasing a protein crucial to helping blood stem cells to mature.

The corollary to this is that if Pi4Ka mutates and begins to produce the protein incorrectly, there is a high risk of contracting leukaemia.

This discovery has huge potential for the early diagnosis of leukaemia - we should now be able to clearly identify when a patient has a high propensity for contracting the disease.

However, there is currently very little we can do for such a patient in terms of treatment until they actually contract it, at which point we can begin the usual process of chemotherapy and stem cell transplantation.

Advance knowledge of the propensity is of somewhat limited advantage – and could even be considered disadvantageous for the patient.

It also raises a number of ethical questions. If we can tell patients that they are at high risk of blood cancer but we can’t help them, how does this affect them psychologically?

There is significant potential for it to cause depression, not only for the patient but also their family. In countries where there is no National Health Service, their health insurance premiums are also likely to rise, or they may even become effectively uninsurable.

Our new knowledge of Pi4Ka’s function is a fundamental step towards eventually developing preventative therapies for leukaemia – but its immediate clinical impact remains to be seen.

Second Opinion

"Is the creation of working muscles from stem cells really a 'world first' breakthrough?"
(The Independent )

What do our experts say?

There’s a little bit of hyperbole in The Independent’s headline “Working muscles grown in lab from skin stem cells in world first”, writes WideCells Group CSO Peter Hollands.

Firstly, muscle tissue has been produced many times before from stem cells. What’s interesting here isn’t that muscle has been produced, it’s that this is the first time that it has been produced in this particular way, using induced pluripotent stem cells.

These are stem cells that have been created from normal, mature cells. Often skin cells are used, because they’re easily accessible. Certain new genes are added to the collected skin cells - usually via a virus, such as the ‘Pax7’ mentioned in the article - and these turn the cell back into a stem cell. This is then known as an induced pluripotent stem cell, or IPSC.

IPSCs have immense potential, as they’re able to create most tissues in the body. In theory, you can apply IPSCs to any disease – although from a practical point of view, researchers are looking initially towards their potential uses in treating particularly problematic conditions such as diabetes and heart disease.

The creation of IPSCs is still a fairly experimental process, and IPSC based treatments are only in clinical trials at this point – there are no routine applications.

But while this report is right to say that “much of stem cells’ potential in clinical practice remains to be seen”, it’s worth noting that IPSCs are likely to be eventually extremely effective in specific applications, even if they aren’t ever universally practical as a treatment.

With that in mind, it’s encouraging to see research projects such as this one coming to fruition.

Second Opinion

"Can we really 'manufacture' stem cells to repair our bodies?"

What do our experts say?

WideCells Group CSO Peter Hollands reviews reports of "a newly FDA-approved platform that can manufacture stem cells by the billions".

What the "automated bioreactor" that this article talks about is doing is something called cell expansion, a process which has been around for many years. The idea isn’t new – but what is interesting is that their approach is slightly unusual.

Normally, cell expansion is carried out manually in a lab, and involves taking cells extracted from a donor and treating them with chemicals which stimulate them to grow and divide.

It appears that in this case, however, the bioreactor automates this process to some extent – and even more intriguingly, it seems that the bioreactor expands mesenchymal stem cells.

Usually, cell expansion work focuses on blood-forming cells, as these are taken usually from cord blood, which provides a limited yield of cells per donor. Mesenchymal cells can be taken from more areas of the body, and aren’t usually expanded in this way.

Responsible for making connective tissue, muscles, and nerves, among other areas, mesenchymal stem cells are becoming more and more useful in treatment as time goes on.

Mesenchymal stem cells also very user friendly for clinicians - they don’t carry the antigens, or "markers", that can cause a patient’s body to reject transplanted cells, and instead are universal – unlike blood-forming stem cells, which require a match between the donor and the patient.

For mass production of stem cells, this makes much more sense.

It will be interesting to see if the bioreactor is easier to work with with and provides more easily replicable results than the manual process in the long term.

Second Opinion

"Herpes virus may help inform treatment planning for stem cell transplants"
(Eureka Alert)

What do our experts say?

Can a common virus help inform treatment planning for stem cell transplant patients? WideCells Group CSO Peter Hollands reviews the research.

Graft versus host disease (GvHD) is an issue for almost all stem cell transplantees to a greater or lesser extent, but a new study demonstrates that a common virus could hold a partial solution.

The human cytomegalovirus (CMV) is a form of the herpes virus that many of us carry. It usually lies dormant, only usually becoming symptomatic during immunosuppression – such as that experienced by stem cell transplantees who have undergone high dose chemo, and have severely limited immune systems as a result.

When that immunosuppression allows CMV to rear its head, it’s also an opportunity for the CMV to potentiate GvHD, making symptoms more acute. That means that patients carrying CMV are much more at risk of severe GvHD than other stem cell tranplantees - but it also implies that through testing for CMV ahead of time, the risk of GvHD could be reduced.

To understand why this is possible, it’s important to know how decisions regarding GvHD treatment are usually made. Following an allogeneic (donor-based) stem cell transplant, doctors will then evaluate whether the patient is suffering from GvHD, if they are, how severely. If it’s judged to be sufficiently severe, antiviral drugs will be prescribed. This study instead proposes that instead of waiting till the post-transplant stage to make a decision regarding antiviral drugs, they are prescribed pre-transplant to all patients who test positive for CMV.

This would mean that the medication is included as standard as part of the other drugs prescribed as part of the transplant protocol.

The overhead in terms of time and cost is relatively low, since CMV is already tested for as a matter of course in all pre-transplant patients – and an antiviral drug is a minimal addition to the already generous number of medications that a transplantee will be receiving as standard.

An interesting study - the risks of the approach it recommends appear minimal and the potential benefits seem high.

Second Opinion

"'Unheard of' results in myeloma CAR-T study: but is it worth the risk?"

What do our experts say?

CAR-T therapy has received a lot of press recently, and this study shows why to some extent, says WideCells Group CSO Peter Hollands.

An immunotherapy, CAR-T treatment calls for the modification of a patient’s T-cells with special proteins which help them to target and fight specific cancer cells.

A not entirely new idea, immunotherapy more broadly has been around for twenty or so years. What’s held it back from becoming mainstream – despite impressive results like those mentioned in this recent study – is the high degree of potential danger that the treatment carries.

As doctors, we always talk about risk versus benefit. Much of the time, the risks outweigh the benefits when it comes to immunotherapy.

CAR-T treatments are potentially fatal due to the high risk of what’s called ‘cytokine release syndrome’.

Cytokines are small proteins which exist in tiny concentrations in the body, but are produced in relatively large amounts by CAR-T cells. If this much higher concentration gets into the bloodstream, this causes issues with vital organs such as the kidney and brain, and can ultimately cause death.

It’s impossible to control this process once it has started – there’s no way of stopping the cytokine or even down-regulating them. This only affects some recipients of CAR-T cells, and we don’t yet know why it doesn’t affect everyone.

However, CAR-T therapy can still make sense for patients who are critically ill and have tried every alternative. Unlike first-line treatments it can offer patients with as little as a month to live a fifty-fifty chance of survival – and it’s understandable that for them the benefits may outweigh the risks.

Second Opinion

"Why old and young muscle stem cells behave differently"
(News Medical)

What do our experts say?

A new study comparing the activity of muscle stem cells in a healthy but elderly body versus those in an injured but young body has concluded that cells in each area work very differently. WideCells Group CSO Peter Hollands responds.

The cells in the elderly body are restricted (they have limited heterogeneity – i.e. they can’t divide very much) while those same cells in an injured younger person are much more active.

This is because the environment for the stem cells in each case is highly distinct. In the younger person’s body, there will likely be cytokine release due to the injury, a protein release which will stimulate the stem cells to grow. In the older person’s body the opposite will likely be true, and the deterioration of the tissue over time will have signalled to the stem cells to slow down or stop working.

The study’s main finding - that muscle stem cells work differently in different environments - might not seem revelatory, and perhaps may even seem like common sense. However, to have this fact scientifically demonstrated represents an important step forward for our understanding of how muscle stem cells might be used for treatment.

Currently muscle stem cells are not used for any type of therapy, and as they were only identified a mere twenty or so years ago, we are still at the very beginning of our understanding of them.

In the future there is the potential for them to perhaps help us treat diseases, such as muscular dystrophy and Charcot-Marie-Tooth disease, as well as to influence anti-aging therapies. Studies such as this one are key to eventually making these things possible.

Second Opinion

"Who nose? Research into repairing olfactory function smells good"
(Science Daily)

What do our experts say?

WideCells Group CSO Peter Hollands examines new research from Tufts University School of Medicine.

The research focuses on what are called induced pluripotent stem cells (iPSCs), a stem cell created from a “normal” non-stem cell through the deliberate introduction of a set of specially chosen genes. Not yet fully understood, research is still ongoing into how iPSCs might be fully harnessed clinically – but their potential for the future treatment of disease is immense.

The experiment here is using iPSCs to repair damaged sense of smell in mice. It’s of particular interest because instead of introducing the 4 genes usually required to create iPSCs from “normal” cells (the “Yamanaka process” referenced in the article), they have managed to simplify the process to require only 2 genes.
This is an interesting variation on the usual processes of creating iPSCs – and part of the key to how they have achieved it may lie in their choice of cell. The traditional “4 gene” process has in the past relied on skin cells or other “ordinary” types of cell, whereas this experiment used cells from the interior of the nose. These nasal cells have a number of special properties, and judging by this research they may have particular potential as raw material for the creation of iPSCs.

iPSCs are currently still at a very experimental stage, and are not yet being produced for clinical treatment. However, their potential is huge both for regenerative medicine and for the study of disease, as iPSCs produced from the cells of sufferers of a condition are invaluable to researchers. This is a fascinating piece of research by Tufts.

Second Opinion

"Amniotic fluid stem cells could be harvested via new caesarean technique "
(New Atlas)

What do our experts say?

It has been known for some time that amniotic fluid contains a large number of very useful stem cells. This is something that our associates in Kolkata have been studying for a number of years, in fact. But the drawback to using them has been the difficulty in reliably extracting them, writes WideCells Group CSO Peter Hollands.

To gather them, a caesarean section is usually necessary. This is already suboptimal, as it is an operation normally performed as an emergency, where time is short and the surgeon’s focus is (quite rightly) on the wellbeing of the mother and baby, leaving little time and attention for the collection of amniotic fluid.

The technique this article talks about is an approach aimed at solving this problem. It discusses a controlled procedure for the extraction of amniotic fluid, which doesn’t affect the caesarean procedure or negatively impact the patient’s safety.

It’s an exciting development - not least because the potential of amniotic fluid for stem cell treatments is great. A technique which allows us to acquire it more easily could help to bring it into wider clinical use.

As an aside, it’s worth noting that while the article points out that amniotic fluid could potentially be a better general source of stem cells than the more commonly used bone marrow or cord blood, this is something of an “apples to oranges” comparison.

Amniotic fluid stem cells are mesenchymal, creating nerves, muscle, bone and other tissue, while cord blood stem cells make only the stem cells in blood. They are complementary, rather than interchangeable.

Second Opinion

"Could stem cells herald a cure for Type 1 diabetes?"
(Medical News Today)

What do our experts say?

Often when we talk about experimental stem cell treatments, we are talking about rebuilding bones and tissue. But this diabetes study focuses on how faulty stem cells can themselves be fixed through the use of a newly formulated protein, dubbed PLD1. WideCells Group CSO Peter Hollands responds.

Diabetes is a complex autoimmune disease, in which the patient’s own immune system begins attacking the insulin producing cells in the pancreas. The usual treatment for this is insulin injections, an imperfect solution that requires patients to self-administer the treatment, with often varying degrees of reliability.

A stem cell-based alternative involves high dose chemotherapy to kill bone marrow before it is restored again via the injection of stem cells, essentially ‘rebooting’ the immune system. Not a popular choice, this uncomfortable and potentially lethal therapy can also be very expensive due to the time patients will be required to spend in hospital.

PLD1 is designed to provide a simpler, cheaper and more effective solution, linking onto the problematic cells caused by diabetes and ‘downregulating’ them to prevent them working. This gives the body an opportunity to repair the damage they’ve caused.

One downside is that PLD1 would effectively be taken by patients as a medicine, and they will need to take it regularly to ensure it keeps working – much as they currently do with insulin injections.

However, its long term effectiveness could potentially be optimised by combining it with stem cell treatment. A cellular cure would mean that the cells continue to exist in the body forever, and there would be no need to continually administer the treatment. A future ‘ultimate treatment’ combining both PLD1 and stem cells could use the protein to initially downregulate the faulty cells, before incorporating donor stem cells to maintain this downregulation and make it permanent, allowing for an eventual tapering off of treatment.

PLD1 seems to have potential for the future – it would be interesting to see whether such a combination of protein and stem cell could be extended across other autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

Second Opinion

"From mice to men? Paraplegic rodents regain movement after stem cell therapy"
(Daily Mail)

What do our experts say?

This article published in the Daily Mail focused on research attempting to regrow the damaged spines of paraplegic rats, which produced positive results – around 60% of the rats tested recovered some movement. The hope is that this insight can be transferred into treatments for paralysed humans. WideCells Group CSO Peter Hollands responds.

Interesting research, but as always, it’s worth bearing in mind that the jump from mice to men is rarely an easy one. On a basic level, the surface area required to rebuild a rat’s spine is far smaller than a human’s. But humans are also far more complex creatures with not only vastly different physiology, but also very different resistance to trauma. This means it is often the case that techniques successfully used on animals are difficult if not impossible to transfer.

Something particularly distinctive about this experiment is that it uses stem cells from human mouths – with the implication that, if this therapy transferred to humans, it may allow the use of stem cells taken from a patient’s mouth to treat that same patient’s spine.

This is distinct from the manner in which stem cell treatments are usually conducted currently, using donor cells from body fat or bone marrow. It could be a significant advantage to be able to use a patient’s own stem cells for treatment, as they are guaranteed to be a perfect match. Additionally, the mouth is an omnipresent and ready supply of stem cells.

There is potential here – the 60% success rate shows promise for the future. But a transfer of this procedure to humans should still be considered uncertain at this stage.

Second Opinion

"Can scientists use human stem cells to build a new rat intestine?"
(The Verge)

What do our experts say?

The Verge reports on research conducted into the possibilities for growing entirely new organs using stem cells, based on a recently conducted study which resulted in the successful creation and transplantation of a rat intestine. WideCells Group CSO Peter Hollands responds.

It’s excellent work, and a fascinating experimental study from a scientist’s point of view – but it’s worth noting that it’s not necessarily an indication that this will be the future of organ transplantation in humans.

Jumping from mice to men is rarely easy, as was found during the early days of IVF research. This initial research in IVF was successfully conducted with rodents relatively simply, but when research switched to humans, it became immensely more complex and challenging. The same is likely to be true here, perhaps to an even greater extent.

Growing a mouse organ may be relatively easy due to the simple expedient of the physical size of a mouse. As a mouse is significantly smaller than a human, the internal organs are composed of a fraction of the amount of tissue compared to a human. There may also be differences in the complexity of the relative tissues. It’s likely that scaling this process up to the required level of tissue for a human organ would be exponentially more difficult.

However, growing new organs is not the only way that patients with Crohn’s and similar diseases might be helped by stem cell research. More straightforward cell therapy – focusing on the repair of the existing organ via stem cells, rather than wholesale replacement – could be an easier path.

Second Opinion

"Are stem cells the next stage in sports medicine?"
(Sports Illustrated)

What do our experts say?

Sports Illustrated report that at the Andrews Institute, Stem Cells are seen as the next stage in sports medicine, Peter Hollands, chief scientific officer, Widecells Group PLC responds.

Sports Illustrated here correctly asserts that stem cell therapy is well suited to sports medicine. The damage caused by sport – effectively post-traumatic – is generally to skeletal components, not dissimilar to the disease-based damage of ailments more well known for their conduciveness to stem cell treatment (such as arthritis).

The promise of stem cell therapy for sports medicine is, according to the article ‘Fewer surgeries. Faster recovery times. Football and basketball players who return to action after torn ACLs in three to four months’. This is a reasonable claim.

However – the article also discusses at length the case of former professional American football player Bart Starr, who is described as suffering from longstanding and debilitating problems following a stroke at age 81, including being bedridden and unable to speak for several months.

He is then described as being able to walk and talk again just three days after his first stem cell injections. After further injections, he is described as having regained most of his physical and mental capability.

The story’s presentation of the case is in danger of giving readers unrealistic expectations. We must bear in mind basic biology at all times when considering stem cell research – when a patient has a longstanding condition, a cure will never be truly instant. These things will always take time and many patients may not see any benefits at all.

The potential of stem cells is very great - but when stories regarding them are not sufficiently grounded in the facts, they’re unhelpful both to potential patients and the stem cell industry’s reputation.

Second Opinion

"How charlatans threaten stem cell research with unproven cures"
(The Guardian)

What do our experts say?

This Guardian article highlights the ongoing global issue with fraudulent clinics claiming to offer validated stem cell therapies, and correctly asserts that not only can this result in tragedy for those exploited, but it also restricts the development of legitimate stem cell therapies.

There are no easy answers on how to prevent fraudulent stem cell treatment – to some extent, the problem is self perpetuating, with an unfortunately ready supply of both vulnerable people desperate for cures and people seeking to exploit that desperation. However, regulatory bodies form a key bulwark against the fraudsters. In the USA and the UK, the FDA and the Human Tissue Authority are particularly tough and effective regulators who are well versed in ensuring that medical treatments are evidence-based.

While the article suggests that the problem of fraudulent treatment has spread to the US and UK, it’s in developing nations that it remains the biggest issue. India has recently taken positive steps against this, with heavy restrictions now placed on the storage of stem cells. This type of regulation is good news for the biotech community globally, as it provides welcome ethical, moral and legal boundaries for legitimate researchers to work within.

Just as important is that the general public are educated about what stem cells can and cannot do. It can be difficult for the average person to distinguish between fraudsters and the real scientists, and addressing this is a major part of Widecells’ work. By offering straightforward, evidence-based opinion, we aim to increase understanding and awareness of not only the facts regarding the enormous potential of stem cell technology, but also the limitations of stem cell technology.

Second Opinion

"Will stem cell therapy help with arthritis?"
(Palm Beach Post)

What do our experts say?

The Palm Beach Post reports that stem cell therapy can help tackle arthritis. Peter Hollands, chief scientific officer, Widecells Group PLC responds.

You may have read this article from a Florida doctor, or versions of it, which outline a standard approach to using stem cells to treat arthritis – but, importantly, there are some areas that he is not comprehensive in covering.

While he is correct in stating that stem cell therapy can be effective for arthritis, he doesn’t place it in the context of more standard treatments such as steroids and/or non steroidal anti-inflammatory drugs. For most patients, these are sufficiently effective, with stem cells required only in more resistant cases – and even in those resistant cases, stem cell therapy is best used as part of a course of treatment including standard treatments.

This is because the inflammation caused by arthritis creates an environment which is unsuitable for stem cell survival – meaning that the stem cells could die when introduced into such an environment, and therefore be ineffective, if injected into an otherwise untreated area.

Also of interest is that he notes that stem cell therapy is considered safe because it is the patient’s own stem cells that are used. In fact, this approach can be less effective and not significantly more unsafe than using donor cells.

This is thanks to the universality of the mesenchymal cells that are usually used for stem cell therapy, donor stem cells are unlikely to be rejected by the body.

In fact, if they are from a young person, they could even be more effective. This is because the older stem cells are, the less effective they are likely to be in treatment.

Particularly in the case of arthritis, where patients tend be older, the treatment will likely have a higher chance of success when using donor cells from a younger person.