Second Opinion

Stem cell research and regenerative medicine is a tricky and fast-changing field - sometimes it is almost impossible to separate between the hope and the hype. Here you can get a Second Opinion from our experts on some of those sensational headlines.

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.