Key result
Allogeneic embryonic stem cell transplantation results in complete graft rejection in ischemic myocardium.
Why the study?
It was uncertain whether differentiation of embryonic stem cells in ischemic myocardium increases their immunogenicity and risk of rejection after transplantation.
Does differentiation of embryonic stem cells increase immunogenicity and rejection in a murine model of ischemic myocardium?
Does differentiation of embryonic stem cells increase immunogenicity and rejection in a murine model of ischemic myocardium?
In vivo differentiation of embryonic stem cells in ischemic myocardium triggers an accelerated and robust immune response, suggesting that clinical stem cell therapies for heart failure may require ongoing immunosuppression.
Answers are grounded in this paper and cite their sources.
Allogeneic ESC grafts in ischemic myocardium may require immunosuppression; leaves open whether differentiation heightens immunogenicity in human pluripotent stem cell derivatives.
BACKGROUND: We investigated whether differentiation of embryonic stem cells (ESCs) in ischemic myocardium enhances their immunogenicity, thereby increasing their chance for rejection. METHODS AND RESULTS: In one series, 129/SvJ-derived mouse ESCs (ES-D3 line) were transplanted by direct myocardial injection (1 x 10(6) cells) into murine hearts of both allogeneic (BALB/c, n=20) and syngeneic (129/SvJ, n=12) recipients after left anterior artery ligation. Hearts were procured at 1, 2, 4, and 8 weeks after ESC transplantation and analyzed by immunohistochemistry to assess immune cell infiltration (CD3, CD4, CD8, B220, CD11c, Mac-1, and Gr-1) and ESC differentiation (hematoxylin and eosin). In a second series (allogeneic n=5, sham n=3), ESC transplantation was performed similarly; however after 2 weeks, left anterior descending artery-ligated and ESC-injected hearts were heterotopically transplanted into naive BALB/c recipients. After an additional 2 weeks, donor hearts were procured and analyzed by immunohistochemistry. In the first series, the size of all ESC grafts remained stable and there was no evidence of ESC differentiation 2 weeks after transplantation; however, after 4 weeks, both allogeneic and syngeneic ESC grafts showed the presence of teratoma. By 8 weeks, surviving ESCs could be detected in the syngeneic but not in the allogeneic group. Mild inflammatory cellular infiltrates were found in allogeneic recipients at 1 and 2 weeks after transplantation, progressing into vigorous infiltration at 4 and 8 weeks. The second series demonstrated similar vigorous infiltration of immune cells as early as 2 weeks after heterotopic transplantation. CONCLUSIONS: In vivo differentiated ESCs elicit an accelerated immune response as compared with undifferentiated ESCs. These data imply that clinical transplantation of allogeneic ESCs or ESC derivatives for treatment of cardiac failure might require immunosuppressive therapy.
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Swijnenburg et al. (2005) studied Ischemic myocardium (n=40). Embryonic stem cell transplantation vs. Syngeneic recipients vs allogeneic recipients; Undifferentiated vs differentiated state was evaluated on Immune cell infiltration and embryonic stem cell differentiation. Transplantation of embryonic stem cells into ischemic murine myocardium resulted in complete rejection (0% survival) in allogeneic hosts by 8 weeks due to accelerated immune responses.
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