Adverse Effects of Cell Transplantation

Immunological Rejection

Autologous transplantation of iPSCs can realize the goal of an immunosuppressive therapy-free method of cell transplantation. In the case of the allogeneic transplantation of iPSCs, control of the immune response of a recipient is a key factor for the successful engraftment of transplanted cardiomyocytes. If the HLA of iPSCs in the bank is matched with that of the recipient, the need for immunosuppressive therapies will be minimized (Morizane et al. 2013). However, non-HLA-matched allogeneic cell transplantation requires a full dose of immunosuppressive therapies. The immunosuppressive therapies will be essentially prescribed in the same way as in heart transplantation, because the appropriate dose of immunosuppressive therapies for cardiac cell transplantation remains unknown. Moreover, immunosuppressive therapies can give rise to other side effects such as severe infection and malignancy.

Arrhythmia

Arrhythmogenicity is the most important potential adverse effect of cell therapies. Myoblasts are notorious in their ability to induce arrhythmia after transplantation (Menasche et al. 2008). This is why myoblasts have their own triggered activity to induce arrhythmia (Itabashi et al. 2005). Human ESCs-induced cardiomyocytes can electrically associate with neonatal rat cardiomyocytes, and become synchronized to beat in vitro (Thompson et al. 2012). However, the arrhythmogenicity of human ESC-derived cardiomyocytes in vivo remains controversial. One report showed that after ESC-derived cardiomyocytes were engrafted to guinea pig hearts and they showed electrical coupling with the host heart (Shiba et al. 2012). By contrast, the same group also reported that ventricular arrhythmia was induced within the first 2

weeks after transplantation to a monkey’s heart, which disappeared one month after cell transplantation (Chong et al. 2014). These data suggest that it will be necessary to closely monitor the heart for arrhythmia after cell transplantation in humans.

 
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