A recent review shows the current state of the industry with regards to using human pluripotent stem cells (hPSCs) to create cells that are useful for the study of, and therapies for, the human heart.
Pluripotent Stem Cells
Stem cells are the cells that form every other cell in the body, and adult humans naturally have native populations of stem cells to replace losses; the depletion of these reserves is stem cell exhaustion, which is one of the hallmarks of aging. To create stem cells from regular (somatic) cells, researchers use a technique called induced pluripotency, which creates induced pluripotent stem cells (iPSCs). However, purely naive, dedifferentiated pluripotent cells, which could create any cell in the body, are only of limited use and are not effective as a therapy. To form specific somatic cell lines, stem cells must first be differentiated into specific types.
This review begins by describing how to use pluripotent cells to create four separate types of cardiomyocytes, the cardiac muscle cells – which are what keep your heart beating – as well as the epicardial cells that form the wall of the heart. It continues by discussing uses for these cells, including studying human development, developing targeted drugs, and replacing damaged cells in patients.
Advances in our understanding of cardiovascular development have provided a roadmap for the directed differentiation of human pluripotent stem cells (hPSCs) to the major cell types found in the heart. In this Perspective, we review the state of the field in generating and maturing cardiovascular cells from hPSCs based on our fundamental understanding of heart development. We then highlight their applications for studying human heart development, modeling disease-performing drug screening, and cell replacement therapy. With the advancements highlighted here, the promise that hPSCs will deliver new treatments for degenerative and debilitating diseases may soon be fulfilled.
Obviously, the most immediate question for ordinary people, particularly people who are at risk of cardiac events or who have already suffered from them, is simple: is it possible to replace damaged heart tissue with cells generated from hPSCs?
The review’s authors name three critical problems that affect the practical use of hPSC-derived cardiomyocytes: mass production, arrhythmias (heart fluctuations) with grafts, and immunorejection. Mass production of cells is difficult, and the study’s authors describe automated bioreactor systems to fill this need. The arrhythmias may be caused by the nature of the early-stage grafts currently being tested, and enriched, purified hPSC grafts without any immature cells are currently in development. Immunorejection, which occurs when the patient’s immune system rejects the organ as a foreign invader, is a known problem with transplants of all kinds, including existing organ transplants. Ideally, iPSCs would be created from the patient’s own cells, but that process is still too difficult and costly for the clinic. Instead, a generic type of allogeneic cell is proposed as the solution, as such a “universal donor” could be used for all patients.
While hPSC-based therapies still have issues that need to be worked out before they are ready for human clinical testing, research in the field proceeds apace; indeed, stem cell research is among the most well-funded, and certainly the most well-known, of therapies that target the hallmarks of aging. We look forward to the day when losses of these critical cells, both stem cells and somatic cells, in the heart and other organs can be replaced through therapies.