Since 2006, Dusko Ilic has discussed the latest developments and news in regenerative medicine and stem cell research in Regenerative Medicine, and since 2019 has summarized his key takeaways each month exclusively for RegMedNet.
In this special edition of his industry updates to celebrate 15 years of Regenerative Medicine, Dusko shares his standout moments and surprises from the last 15 years in the field, and looks into his crystal ball about what the next 15 may hold.
“It took me by surprise that 15 years had passed since my first Industry Report. Time flies, indeed.”
What happened in the industry that you were expecting?
The rise of mesenchymal stromal/stem cells (MSCs) and a growing list of their nearly magical properties took me by surprise.
I believe in science and I always wanted to see hard proof supporting the claims. For years, there was rarely any; it was inevitable that the MSC hype would end and people would have to embrace the reality of what these cells can or cannot do. However, papers deciphering MSC mechanism of action started coming out. Understanding of how to control their immunomodulatory potential has established MSCs as an efficient therapy for acute inflammatory diseases, such as graft-versus-host-disease.
What happened that surprised you?
The arrival of chimeric antigen receptor (CAR)-T and NK cell-based therapies was something that I did not see coming. It could be just ignorance, because I am not an immunologist and did not follow the field closely. However, even more surprising was how quickly big pharma has jumped on the bandwagon and taken over the field. With large injections of capital, in a few years the field has blossomed.
What have been your standout moments from the last 15 years?
For me, some standout moments in the last 15 years of cellular therapy are: the fall of Geron Corporation (CA, USA), the rise of human embryonic stem cell (hESC)-based therapy for macular degeneration of the retina and the first clinical trials with induced pluripotent stem cell (iPSC)-derived cells in Japan.
Geron Corporation, a Silicon Valley company, was a pioneer in development of hESC-based therapies. Geron filed a 21,000-page Investigational New Drug (IND) application with the FDA and, after a long struggle, finally got a green light to start the trial in spinal cord injury. The first patient was treated at the Shepherd Center in Atlanta (USA) in October 2010. With all the hype, positive and negative, about the use of hESCs in regenerative medicine, the results of the trial were highly anticipated.
Even though the trial was about the safety, not efficiency, the public and investors expected that the treated patients would walk shortly after the treatment. Of course, this did not happen and Geron’s stock dropped nearly 60% in nine months. In spite of the safety results fulfilling all expectations, they had to give up on their stem cell program. That was a shock for all of us working with hESCs and we became seriously worried that the field may not recover for many years.
Robert Lanza and Irina Klimanskaya changed that in the summer of 2011. Their hESC-derived retinal pigment epithelial (RPE) cells become the first hESC-based therapy that successfully demonstrated clinical benefits in clinical trials. Macular degeneration of the retina was a much better choice for pioneering a new treatment than spinal cord injury. Other companies followed and today, ten years on, we have more than 20 hESC-based clinical trials worldwide in diseases of the eye and adnexa.
Masayo Takahashi from the Riken Centre for Developmental Biology (Kobe, Japan) seized the opportunity and initiated the first-in-man study with iPSC-derived RPE cells. The indication was the same – macular degeneration of the retina. Today, there are about 20 ongoing iPSC-based clinical trials worldwide for more than 10 indications.
Looking into your regenerative medicine crystal ball, what does the next 15 years hold?
Predictions of future development are, in general, unrewarding. I would still dare to make one, which is relatively safe. Lack of ethical controversy has made iPSCs more appealing than hESCs for drug discovery and toxicology-related studies. In years to come, I believe iPSCs will also take over from hESCs in clinical applications. The results of current hESC-based clinical trials are setting a gold standard for future iPSC-based cellular therapy.
Dusko Ilic is a Senior Lecturer in stem cell science, coordinator of the cross-divisional postgraduate program in stem cells and regenerative medicine, and Head of the Induced Pluripotent Stem Cell Core Facility at King’s College London (London, UK). He is also Head of the Assisted Conception Unit’s Human Embryonic Laboratories at Guy’s Hospital (London, UK). He is also a member of the editorial board of the journal Regenerative Medicine, where he writes the Industry Report, a regular feature compiling information from non-academic institutions in the field of stem cells and regenerative medicine.