Pluripotent Stem Cell Technologies for Cardiac Recovery: An Interview with Professor Winston Shim

Michelle Maxwell, SelectScience Editor, spoke with Adjunct Assistant Professor Winston Shim, Principal Investigator of Regenerative Medicine at the National Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore. Prof. Shim, who is recognized for focusing on functional recovery of the heart utilizing stem cells, jointly hosted a workshop at the National Heart Centre with Thermo Fisher Scientific to provide basic research and clinical scientists with the latest in pluripotent stem cell technologies.

Can you describe your work at the National Heart Research Institute Singapore (NHRIS), and National Heart Centre Singapore (NHCS)? How does the use of pluripotent stem cells (iPSC) help with this research?
Regenerative medicine is one of the key research themes at NHRIS. We study human cardiomyocytes to understand diseases affecting the human heart, in particular the area of congenital heart disease in cardiac arrhythmia and channelopathies, such as long QT syndrome, and structural defects, such as Marfan and hypoplastic left heart syndrome. As cardiomyocytes from patients are terminally differentiated cells that are not proliferative and are not accessible due to ethical concerns, we utilize induced pluripotent stem cells generated from donated skin fibroblasts to generate cardiomyocytes that manifest the same disease phenotypes of the patients. With the availability of human disease models in the petri dish, we can examine the biochemical and physiological changes leading up to the disease pathology in their cardiomyocytes, and this offers us a rare opportunity to understand the molecular mechanisms involved in disease manifestation. It is also an unprecedented window for us to examine progression of the disease and to provide us an avenue to safely test new interventions in laboratory to reverse the disease without ever jeopardizing patient safety.

Could you give our members a brief overview of the stem cell workshop you hosted with Thermo Fisher?
Pluripotent stem cells are technically challenging to maintain in the laboratory, and their directed differentiation towards specific cell types that are useful for different study disciplines is not always a straightforward process. We have a longstanding tradition of sharing knowledge and encouraging frank exchanges between diverse participants in the stem cell field. Our workshops are organized in a small group setting, with lectures and didactic sessions to encourage hands-on exposure for every participant. Throughout the workshop, participants are given ample opportunities to participate in every aspect of pluripotent stem cell culture, including examination, maintenance and passaging of the culture. This maximizes the exchange of detailed knowledge between participants and trainers on state-of-the-art techniques used in stem cell technology. The workshops also serve as a networking platform for researchers to meet potential collaborators.

Can you elaborate on any of the technologies and products available that help with pluripotent stem cell research?
To most researchers, pluripotent stem cell research calls for hassle-free generation of pluripotent stem cells, maintenance of undifferentiated cells in tip-top condition and controlled differentiation to desired cell types for downstream assays and applications. Techniques and products that help in these key aspects are most appreciated by researchers in this field. In cardiovascular medicine research, for example, we are most interested in the ability to differentiate pluripotent stem cells towards high yield and high purity cardiomyocytes consistently, and this has long been a bottleneck in this field. To address this constraint, our researchers have developed an exceptionally robust cardiomyocyte differentiation protocol that works with more than 20 different human pluripotent stem cell lines, derived from various sources and methods of reprogramming to meet our research needs. The Epi5™ Episomal iPSC Reprogramming Kit is suitable for all stages of iPSC research, providing transgene-free and viral-free reprogramming from basic to pre-clinical research.

How are iPSCs used in other areas such as stem cell therapy, drug discovery screening and pharmaceutical testing/safety?
The advent of iPSCs has enabled a whole new paradigm that empowers the development of new knowledge, novel applications and revolutionary technologies. Assessment and screening platforms such as microelectrode arrays, automated patch clamps (such as the SyncroPatch 96), high content and throughput screenings are becoming an integral part of the complete workflow in drug screening and pharmaceutical safety testing. Together with the ability to generate patient-specific cardiomyocytes and producing them on a large scale for stem cell therapy, the field is ushering in an era of stratified medicine and regenerative medicine that starts in a petri dish and progresses to testing in traditional assays, such as preclinical animal experiments, for safety and efficacy. This opens a previously unavailable avenue to explore the development of a cost-effective model for personalized medicine.

Where do you see the future of iPSCs and the technology used for research, and in particular cardiac based research?
iPSCs have great potential in cardiovascular medicine research. The seminar work on inherited channelopathy using patient-specific cardiomyocytes heralds our deeper appreciation of the disease manifestation. It also paves the way for targeted drug development with a better risk-adjusted safety profile. In addition, the availability of the iPSC platform expedites the development of new classes of drugs, a faster roadmap for drug discovery, and a new generation of novel therapies for heart disease.