The path to the clinic is a slow and arduous activity, frustrating not only to the researcher and patient, but investors and biotech companies. Successful clinical translation of technologies requires a balance of science, streamlined translation and funding. To develop fantastic science and then realise the most important components cannot be adapted to the clinical environment is as disastrous as having a great product but no cash to get it past the post. The fruitful interaction of researchers, companies and clinics will save a lot of pain in streamlining technologies to patients. Thus, it was nice to see an ISSCR 2015 plenary session on stem cell therapies including companies StemCells, Inc. and ViaCyte, Inc. The topics were a good spread of autologous and allogeneic cell sources as well as therapies directed at inflammation and immune reactions versus integrative cell replacement technologies.
StemCells, Inc. presented progress in clinical trials with allogeneic neural stem cells in brain, spinal cord and eye disorders. As is the reality for companies giving talks some data and beautiful pictures is not disclosed. Though there were no revolutionary data sets on efficacy, what was clear was that grafts could persist 1.5 years post removal of immunosuppression (this was determined with HLA-mismatch begging the development of a Shinya Yamanaka style allogeneic HLA cell bank). It should not be a surprise that there were no amazing efficacy leaps in these first trials. There would be a lot of luck in getting the right cell, the right dose and the right transplantation method in the first go. Even the development of reliable measures of graft behaviour and efficacy will take time to develop and standardise.
Doug Melton was clear to state that they “haven’t (just) done an academic study”. That while they are not yet in the clinic and even though they present a more classical academic study, showing a complex defined differentiation and detailed functional analyses, that they recognise the importance of not just talking the talk but walking the walk. Doug presented their in-vitro beta-cell body technology that show functional characteristics equivalent to, if not better than, cadaveric islets. They were able to upscale this technology and are now on the prowl for encapsulation technologies to move into the clinical space, which will happen through their new start-up Semma Therapeutics.
It’s always nice to hear an Aussie accent ;), giving additional benefits to listening to Alan Robins present the progress of ViaCyte in clinical trials of their pancreatic progenitor and encapsulation technologies. Following on from Doug, Alan made a couple of comments to assure the audience that there was a lot of vigorous science behind their technology, the curse of not being able to disclose and thus somewhat unfairly being seen as less careful. The ViaCyte technology is based on the major phase of expansion in pluripotent cells followed by mass differentiation and subsequent encapsulation. Interestingly in their pre-clinical animals studies the grafts were able to regulate insulin levels at the standard human blood concentrations, indicating not only functionality but also species specific functionality.
Katarina Le Blanc presented her work on MSCs for GVHD, diabetes and vocal cord scarring. Somewhat disappointingly I heard the comments of someone leaving this talk with the all too common disregard that MSC technologies are inferior to pluripotent technologies rather than recognising them as complementary technologies. Katarina showed epithelial cell death and inflammatory markers were reduced with maximal effect at 3 weeks after IV injection for GVHD, even though they also prove that IV infused cells have mostly disappeared already at 3 days post infusion. She also showed that while coagulation and complement cascades are activated in response to IV infusion of MSCs blood clotting is not a common occurrence. The risk of clotting was cell number, dose and passage number dependent, which is a little scary when many autologous therapy clinics do not standardise the cell number they IV inject.
It’s great to see both academics and companies being recognised as the drivers of cellular therapies. Working in a stem cell company myself, I was surprised 2 years in a row to see talks from academics about skeletal muscle differentiation protocols that do not come close to our technology. It’s somewhat understandable that when it is not possible to disclose a lot of details of your research, the companies are often not taken seriously and are relegated to paid presentations during the lunch break. It is fantastic however, to see positive movement in reputable exposure for the companies attempting to drive research to patients.