It is estimated that by 2030 more than 23 million people will die every year as a result of cardiovascular disease, according to reports by the World Health Organization. In addition to efforts for disease prevention, multiple therapeutic approaches are under development to treat cardiovascular disease, including stem cell therapies. Stem Cell Research & Therapy therefore took the opportunity to present a series of articles on cardiovascular regeneration, with the aim of reviewing the latest stem cell-based approaches for disease modelling, drug discovery and myocardial repair. Guest Editor of this special series, Ronald Li from the University of Hong Kong, tells us more about the hurdles and hopes in stem cell-based treatments for cardiovascular medicine.
Ronald Li is Professor of Stem Cell Biology and Regenerative Medicine at the University of Hong Kong, where he serves as Director of the Stem Cell & Regenerative Medicine Consortium. He is also a senior faculty member in cardiology at the Mount Sinai School of Medicine, USA. Li previously held positions in the USA at the University of California, Davis, the Institute of Pediatric Regenerative Medicine at the Shriners Hospital for Children, and Johns Hopkins University. During his time at the University of California, Davis, USA, he led the Human Embryonic Stem Cell Consortium. His current research interests lie in electrophysiology, cardiac differentiation and the development of a library of ‘custom-tailored’ human heart cells.
How did you become interested in cardiology?
As a student, I somehow became interested in how electricity flows through a class of intriguing membrane-bound signalling proteins called ion channels. The heart and the central nervous system were among the best studied organ systems for their bioelectrical properties. The discoveries of human cardiac ion channel mutations that underlie arrhythmias at that time further heralded a new era of cardiac electrophysiology. Soon after, human embryonic stem cells were discovered and shown to be able to differentiate into de novo human heart cells. It was for these reasons that I made heart regeneration my chosen discipline.
What makes the heart a good candidate for regenerative medicine?
It depends on how you define a ‘good’ candidate. There are other organs such as the eye that are more immediately approachable because they are immune-privileged and require relatively less cells to bring forth clinical benefits. But the heart is definitely one of the organ systems that can significantly benefit from advances in regenerative medicine due to the prevalence and clinical consequences of heart diseases from arrhythmias to late-stage heart failure, and for the simple fact that heart cells do not have the innate capacity to regenerate once they are lost (e.g. by myocardial infarction). As such, there are no cures for many of the conditions, and the current treatments are only palliative. Stem cell-based therapies are going to change this paradigm.
In one of the first reviews in the series Liao and Tse discuss the pros and cons of multipotent (adult) and pluripotent stem cells for heart regeneration. Which do you think have the most potential?
Both adult and pluripotent stem cells have their pros and cons. Adult stem cells can be autologous but their abilities to proliferate and regenerate are typically limited, unlike pluripotent stem cells (PSC). Personally, I am an optimist for PSC technologies, and can totally see that such will lead to different bio-artificial organ or tissue banks in the not too distant future for in vitro diagnostics and even for transplantation. Objectively, I think that the jury is still out, and the winner does not have to be the one that leads to the first trial but the one that causes the best clinical outcomes, reproducibly. The two stem cell types do not have to be mutually exclusive. It’s even good for patients to have options, depending on the particular conditions.
Technological breakthroughs will be necessary to produce stem cells for clinical applications on a commercial scale. From what areas do you see these breakthroughs coming from?
Mass production and quality control of cells, their delivery methods and subsequent functional integration after transplantation. Many of these are really engineering problems, and hopefully, their solutions can be provided by engineering means.
In addition to the potential of using stem cells for the regeneration of cardiac tissue, how else can stem cells contribute to cardiovascular medicine?
Clinical applications are going to take time before they will become widely accepted routines because there are defined processes that need to be followed. The fact that different countries have different policies and standards complicates the matter even more. But this does not mean that PSC technologies cannot be practically applied for the public community to immediately benefit. Indeed, they are great in vitro diagnostic tools for drug discovery, toxicity screening and disease modelling, and are particularly useful for studying genetic diversity such as those related to different ethnicities. Imagine that if a new drug candidate does not work or has unacceptable side effects, we will want to find out sooner or even before they are given to humans so more time and resources can be focused on their modifications or identification of better candidates.
What progress do you think would have been made in cardiovascular regeneration in the next 10 years?
Personalised stem cell-based heart tissue regeneration.