Interview with Antoni Bayés-Genís an eminent clinical researcher

Application of stem cells, is it too early for general clinical use? Are there too many unresolved problems and uncertainties?
The promise of stem cell therapy is an area of tremendous excitement for over a decade. The accumulated human experience up to date suggests that stem cells are safe when delivered in liquid solutions (either intracoronary or intramyocardial). In terms of real benefit the data are modest and we do not have yet a large clinical trial with true clinical outcomes (mortality ± hospitalizations ± quality of life). There are many unresolved issues that unfortunately have not yet a clear answer: which are the best suited cells for cardiac regeneration? Do we need exogenous stem cells or activate the endogenous cardiac progenitors? How can we attract these cells into the myocardium? There is a strong need for young talents to participate in this research area to provide a fresh and novel approach to cardiac regeneration.

Is there a future for autologous stem cell transplantation?  Which are the main hurdles that need to be overcome?
My perspective here is dual as a Janus-faced. In one face I believe that allogeneic MSCs (either from adult or fetal origin) do have a future, since they have proved to be safe and do not activate an immunogenic response. This places them in a good pole position for clinical testing right now. On the other, there is a great promise with the use of autologous iPS. Probably not uncommitted iPS, but rather cardiomyocyte-derived iPS. Technology is evolving quickly to remove the need for a viral use and to provide mature synchronous cardiocytes. There is a lot of enthusiasm on the potential use of these committed iPS in human cardiac diseases.

What are your thoughts regarding the development and application of technology (bioengineering) for improve culture, propagation, survival, homing and engraftment of stem cells?
Given the limited engraftment and response to the conventional stem cell therapy, the need for advanced therapies including cardiac tissue engineering is evolving quickly. In the year 2015 already 700 entries can be found in PubMed for cardiac tissue engineering. Both natural and artificial scaffolds are being refined to be gentler with the seeded cells, and the pre-clinical experimentation is moving from mice to swine at a quick pace. Ultimately, there is the concept of organogenesis which also holds a lot of promise. We have already performed swine experimentation with myocardial bioprosthesis made of decellularized myocardium and allogeneic MSCs with promising results, and relative ease to clinical translation. I believe the cardiac graft of the future will incorporate a matrix, cells, growth factors/cytokines, and eventually will be biofabricated using a 3D bioprinter.

From your perspective, which stem cell type ultimately holds the greatest promise?
At present and after 15 years of active experimentation my answer remains inconclusive. I have expectations in MSCs both adipose-derived and from fetal tissues (placenta, umbilical cord, etc). In point of fact, we found that cardiac adipose tissue-derived progenitor cells were particularly well suited for cardiac regeneration. I also hope that we can activate cardiac resident cells to migrate within the myocardium and replace the damaged areas. Certainly, we all keep an eye on iPS and ESCs.

What advice would you give to a junior researcher looking to start a career in the field of stem cell research?
First, this is an exciting area of research with the potential to change the way we do medicine in the future. Second, a career in stem cell research is evolving towards a biomedical engineering career. My advice to young researchers is to have an open mind to non-biological approaches that may work alone or in combination with stem cells. Third, have a lot of passion in what you do because the road to success may be very bumpy. Forth, always be honest with the data you get; even if it is not what you expected is as valid. Fifth, think big. Sixth, don’t stop when you are tired, stop when you’re done. This is an endurance race!!

Any final thoughts?
Yes, I strongly recommend young researchers to follow their instinct.
“Instinct is something which transcends knowledge. We have, undoubtedly, certain finer fibers that enable us to perceive truths when logical deduction or any other willful effort of the brain is futile” Nicola Tesla.