Cardiac muscle cells (cardiomyocytes) derived from the stem cells of one macaque can be used to regenerate the damaged hearts of other macaques, reports a Nature paper published online this week. The transplanted cells electrically integrate with the cardiomyocytes of the host and improve the ability of the damaged heart to contract, with no sign of rejection by the recipient’s immune system. However, the technique also leads to an increased incidence of irregular heartbeats.
Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) show promise for transplantation into and repair of damaged hearts. Although iPSC-CMs created from a patient’s own cells have a major advantage over donor iPSC-CMs in that they are compatible with the patient’s immune system, they are also associated with challenges related to manufacturing and regulation. Creating iPSC-CMs from a donor provides a potential solution to these challenges, but donor iPSC-CMs can illicit an immune response in the recipient, possibly causing the transplanted iPSC-CMs to be rejected.
To overcome this problem, Yuji Shiba and colleagues ensured that a key cell-surface protein used by the immune system to recognize foreign cells was matched between the donor and recipient. They generated iPSC-CMs from skin cells of a donor macaque and transplanted these iPSC-CMs into the hearts of five recipient animals that had each suffered an induced heart attack. The authors report that, using mild immunosuppression, the iPSC-CMs can engraft and survive for 12 weeks, with the engrafted cells electrically coupling with host cardiomyocytes and improving cardiac contractile function.
However, the authors note that the treatment also led to an increased incidence of arrhythmias, as observed in a previous study using embryonic-stem-cell-derived cardiomyocyte transplantation into non-human primate hearts. The findings demonstrate that transplantation of immunologically matched iPSC-CMs from a donor to a recipient animal can provide long-term graft survival in the infarcted non-human primate heart, but that further research to control post-transplant arrhythmias is necessary before the therapy can be translated to the clinic.
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