Technology Platforms for Heart Regenerative Therapy Using Pluripotent Stem Cells
Heart failure is a common, disabling, and deadly disease affecting over 23 million people worldwide. The prevalence of this disease continues to increase each year despite substantial advances in pharmacological treatments and mechanical assistance. Heart transplantation is the ultimate treatment for severe refractory heart failure. However, it benefits only a small proportion of patients because of the limited number of donors and significant surgical invasion. Heart regenerative-cell therapy thus presents a promising alternative strategy. Pluripotent stem cells (PSCs) including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) could provide mass-production cell sources for such therapies because they can theoretically self-renew indefinitely. Currently, iPSCs are intensively studied because they are more easily derived from somatic cells than ESCs, carry fewer ethical concerns, and have potentially wider applications including autologous cell therapies. However, technical concerns remain with the use of iPSCs.
A xenofree culture system would be ideal for therapeutically applied PSCs, although such culture systems still have limited compatibility with many cell lines. To improve this, we have developed a simple preparation method for culturing autogeneic feeder cells from each PSC line. Potential tumorigenicity also remains a major obstacle to clinical applications for PSCs. For heart regenerative therapy, purifying differentiated cardiomyocytes would be a reasonable approach for eliminating undifferentiated cells and retaining only therapeutic cells. To this end, we have established a nongenetic method for PSC purification using mitochondrial marker dyes. Finally, transplantation and efficient survival of PSC-derived cardiomyocytes has proven difficult and it depends on the method of cell preparation. Recently, washout and anoikis were identified as factors underlying the disappearance of injected cardiomyocytes from heart. We have now also developed a simple and efficient way to achieve over 90% survival of injected cardiomyocytes in the host heart. This chapter will lastly discuss new obstacles and future divergent directions for PSCs in heart regenerative therapy.
KeywordsPluripotent Stem Cell Embryoid Body Mammalian Heart Heart Regeneration Host Myocardium
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