In this Exclusive Interview transcript, Jon Odorico talks with Diabetes in Control about advances in the work with stem cell derived beta cells.
Odorico: John Odorico, Professor of Surgery at the University of Wisconsin, Madison School of Medicine and Public Health.
What recent advances have been achieved in the stem cell derived beta cells arena? A number of them over the last few years. Firstly, in 2014, some very important publications which showed improved differentiation of the cells through an in vitro protocol to getting to more phenotypically and functionally mature beta cells.
In addition, there have been some important encapsulation advances too. In the field of micro- and macro-encapsulation – delivering better oxygen and having better survival of the cells.
Many of the recent advances were discussed and presented at a recent stem cell meeting in Boston where 170 delegates were brought together from a dozen countries at a stem cell-derived beta cell Key Opinions Leaders Meeting sponsored by the International Pancreas and Islet Transplant Association, the Transplantation Society, JDRF (Juvenile Diabetes Research Foundation), and the Harvard Stem Cell Institute; some real exciting advances were presented at that conference last month.
ViaCyte Stem Cell Trial
Odorico: A recent trial – first-in-human trial – was just completed by ViaCyte, which is a combination of a pancreatic progenitor cell population and a proprietary Encaptra macroencapsulation device. The results are very interesting. I think we learned a lot from that trial, although the results were not as robust as we would have hoped. First of all, I’m not affiliated with ViaCyte at all, I’m just reporting unpublished results that were presented at this Key Opinion Leaders Meeting. Secreted insulin was not observed in the blood of the patients. The sentinel devices were predictive of the larger devices in terms of the differentiation. But the number of differentiated insulin-expressing cells were not observed that were hoped to be observed in the histology in the devices at explant. However, there was no donor specific antibodies or autoantibodies detected in these recipients. There was some fibrotic capsule, so there are still some hurdles and the company is designing next phase trials with PEC-Direct trial.
Challenges of Translating Stem Cell-Derived Beta Cells to the Clinic
Odorico: There are a number of challenges still. They include improving functionality yet to a more mature population. We still are missing an understanding of some of the key signals at the last phase of development that are probably important for robust-functionally developed islet-like clusters and beta cells. In addition, we need to better understand the immunogenicity of the cells, both in the autologous cells and for allogeneic cells, and, in the autoimmune setting as well as in the allogenic setting.
Finally, we really need to improve the transplant site; the liver is not an ideal site and many groups are working on sites including the omentum, subcutaneous, prevascularized sites, intramuscular sites – sites that are potentially retrievable. That’s important when thinking about stem cells and the possibility of rogue cells.
Who is Involved in Research of Stem Cell-Derived Beta Cells?
Odorico: The work in this arena of stem cell-derived beta cells has now moved beyond academics. There are more and more academic labs interested and involved in doing good research in this area. But of late, several biotech companies have spun out of work in this area. They include Semma Therapeutics, Novo Nordisk, EvoTech Santa Fe, Regenerative Medical Solutions, and several others, including stem cell encapsulation technologies that are being promoted by Sigilon as well as Beta-O2.
What are Researchers Doing to Tackle These Challenges?
Odorico: With the challenges I mentioned, academic and also industry scientists are approaching each of these individual aspects, including immunogenicity, tumorgenicity, transplant sites and improved functionality and a variety of research is going on in those areas. For example, people are looking at what causes cell death after transplantation and people are understanding that there are nutritional deficits and hypoxia is playing a role as well as cytokines in those areas.