1. Prof. Hollands, we are happy that you agreed to this interview. Regenerative Medicine should be featured by the big authorities in the field such as you. Could you describe your professional biography as a clinical scientist?
First of all thank you for asking for this interview, it is always a pleasure to talk about stem cells and regenerative medicine. My interest in stem cells dates back to my undergraduate days but my first official work on stem cells was my PhD at Cambridge University in the early 1980’s. My supervisor was Prof Sir Bob Edwards FRS who received the Nobel prize for his work in IVF and he was also very passionate about stem cells. My PhD research focused on the early post-implantation haemopoietic stem cells in the mouse and the way in which they could be harvested and used to treat blood disease in other mice. Since that time, I have worked in both IVF and Regenerative Medicine in the private sector and the NHS and been involved in teaching and research in stem cell technology in various UK Universities. I have also worked in Canada and Nigeria and I am currently working with colleagues to create a unique, cutting edge stem cell clinic in the UK on which more news will follow shortly. This clinic will operate to the highest possible international standards and under all of the relevant regulations.
2. After many years of knowledge and research (basic/Clinical) as well as unproven clinical experiences in the field stem cells, why don’t we have reasonable number of Approved cell-based products?
This is a very good question. Firstly, we must not forget the fantastic work done in bone marrow, peripheral blood and cord blood stem cell transplantation. These are often forgotten in the Regenerative Medicine debate but they of course represent the first and so far best procedures in Regenerative Medicine.
Apart from these fantastic achievements, the rest of stem cell technology has been riddled with media confusion, hype, misinformation and even scientific fraud. This results in mistrust in the stem cell world and more importantly a public conception that stem cell technology is in some way ‘dangerous’. Perhaps the biggest initial hype came from embryonic stem cells. In my opinion these have no significant future in Regenerative Medicine because of regulatory issues and also because of the fact that the number of embryonic stem cells available for therapy is relatively very small.
The commercial side of stem cell technology (stem cell ‘clinics’ and so on) have up to now only damaged the understanding and reputation of Regenerative Medicine. Many such ‘clinics’ deliberately seek to mislead their patients and some have even caused life-changing damage to their unfortunate patients.
All of these things together come together to create a very large black cloud over Regenerative Medicine. If I can leave any legacy at all to Regenerative Medicine I would like it to be that I was instrumental on putting Regenerative Medicine back on course as a safe and effective form of treatment.
3. What are the biggest strength and weakness in research and clinical practice of stem cell therapy?
The basic research in stem cell technology is, in general terms, extremely strong. We have numerous stem cell labs producing excellent basic science. The weakness in some of this research is that it lacks focus and some of it continues to follow routes which have no visible clinical applications. If we are to progress in Regenerative Medicine the research must be highly focused on getting the technology to the clinic and creating safe and effective procedures.
The clinical practice in bone marrow, peripheral blood and cord blood stem cell transplantation is excellent and beyond criticism. Clinical practice in the rest of Regenerative Medicine is at best poor and at times dangerous. The safety and efficacy of some stem cell ‘treatments’ is unknown. Ideally, we need an international regulatory authority to enforce good practice but this would be very expensive to achieve. The Human Tissue Authority (HTA) in the UK and the Food and Drug Administration (FDA) in the USA do a good job but their global remit does not exist. An organisation with a global remit on stem cell technology is needed, perhaps the World Health Organisation (WHO) could become more active in the regulation of stem cell technology?
4. What are the challenges in clinical application and commercialization of stem cell therapy? How we can overcome them?
The clinical application and commercialization of stem cell therapy has many problems. These include deliberately seeking to deceive patients, offering unsafe and untested treatments, charging large amounts of money for treatments and perhaps worst of all operating overseas or offshore where no regulation exists. The commercial use of stem cells on a global scale is currently very unsafe to patients. Patients who seek stem cell treatments are often very vulnerable after traditional medicine has failed to help. This combination of unethical practitioners and vulnerable patients is a perfect storm for the significant loss of money by patients and potentially life-threatening complications for patients. This must stop. Patient safety must always be paramount.
The solution is Regulation but on a global scale, not just a local scale.
It is also essential to use the right stem cell, at the right time and in the right place. Too often, for example, MSC have been injected intravenously with a view to having some therapeutic benefit to neurodegenerative disease. This makes no sense at all. Intravenous MSC will go no further than the lungs for the simple reason of their size.
5. Considering the limitation in cord blood volume, do you believe there will be any room for autologous transplantation (if donating child being an adult)? Or do you imagine another autologous application?
It is well known that a single cord blood unit only contains enough stem cells to treat a patient weighing up to about 30Kg. This problem can be resolved by double or even triple transplantation or in the future routine cell expansion may be possible.
Cord blood also contains good numbers of Very Small Embryonic Like (VSEL) stem cells which could in the future be a possible autologous use for these stem cells.
6. In your point of view what will be the future of stem cell therapy? Autologous? Allogeneic? Non stem cell-based therapy (somatic) will take over? Gene therapy?
Allogeneic stem cell transplantation is safe and effective when using bone marrow, peripheral blood and cord blood stem cells for blood disorders. I cannot see this changing and the routine utility may even increase when these stem cells are used to treat such diseases as multiple sclerosis.
In terms of Regenerative Medicine I think that autologous stem cells will be the most important especially adipose tissue MSC and peripheral blood VSEL stem cells. The only possible drawback is that these cells age with the patient and may as a result be less effective in an older patient. It may be possible that collecting and storing these cells for use in later life could be a useful option.
Non-cell based therapy such as exosomes are interesting but once again they currently suffer from a lot of hype and mis-information.
Gene therapy is making slow but sure progress and I am sure that this will be in routine clinical practice in the years to come.
It is also important to remember such technology as cord blood plasma which may be helpful in neurodegenerative disease.
7. It seems that stem cell therapy is following the same fate as Gene therapy. Sharp raise then sharp fall then plateau, how we can optimize our expectation and make realistic understanding from this field? Where is the problem?
Stem cell technology will develop well if we remove mis-information, hype, poor journalism and regain the confidence of healthcare professionals and patients. This is easier said than done!
The route to these changes will be strict regulation of the global stem cell industry, translation of technology from the laboratory to the clinic and good outcomes from clinical trials. Everything we do in Regenerative Medicine must be evidence based.
8. Do you believe that regenerative therapy will take a strong position in geriatric medicine?
Yes, although I am still skeptical about ‘anti-ageing’ proposals coming from some people. That aside, the diseases suffered by the elderly, especially neurodegenerative diseases and osteoarthritis, have already shown some promise and will no doubt in the future come into routine clinical practice.
9. Your expertise in quality management and safety in stem cell technology is very much appreciated in a field that is new and on the edge of science. However, do you think more strict regulations need to be applied especially in private clinics where stem cells are used – either from fat tissue or bone marrow?
Regulation in stem cell technology is critical to ensure patient safety. This is the case in all emerging medical technologies and critically important in Regenerative Medicine.
The situation regarding private ‘stem cell clinics’ is very serious. Most operate without any regulation at all meaning that the quality and safety of their treatments is either very poor or downright dangerous. Existing regulatory authorities try their best but, on a global scale, vulnerable patients are still at very high risk and action is desperately needed.
The other way to tackle this of course is to educate potential patients directly about the pros and cons stem cell technology. I am trying to do this in my book ‘The Regeneration Promise’ which will be published in the Autumn of 2020.
10. Some scientist believes that the limiting /restricting regulations by the authority in the field of cell therapy is overindulgence, which is not comparable with similar chemical or biotech products? What do you think? Doesn’t this overtreatment suppress the innovation and progress in the field?
No. This is a poor argument often put forward by private clinics to make their lives and profits easier. It is totally wrong. Regulation is the only way in which we can protect patients at the moment (patient education in the future may help) and it must be developed globally. The research and development side is regulated but less so than the clinical applications. The research regulation in no way hinders the development of new basic knowledge.