Immunological barriers to stem-cell based cardiac repair

Abstract

Repair of damaged myocardium with pluripotent stem cell derived cardiomyocytes is becoming increasingly more feasible. Developments in stem cell research emphasize the need to address the foreseeable problem of immune rejection following transplantation. Pluripotent stem cell (PSC) derived cardiomyocytes have unique immune characteristics, some of which are not advantageous for transplantation. Here we review the possible mechanisms of PSC-derived cardiomyocytes rejection, summarize the current knowledge pertaining to immunogenicity of such cells and describe the existing controversies. Myocardial graft rejection can be reduced by modifying PSCs prior to their differentiation into cardiomyocytes. Overall, this approach facilitates the development of universal donor stem cells suitable for the regeneration of many different tissue types.

Fig. 1

Schematic representation of direct and indirect recognition of donor antigens to the recipient T cells

Fig. 2

Cartoon illustrating trends of MHC-I expression and NK susceptibility observed upon differentiation of pluripotent stem cells

Fig. 3

Top Panel: Immunostaining of mouse ESC-derived cardiomyocytes (LONZA, catalog number XCAC-1010N). Bottom panel: ESC-derived cardiomyocytes were pretreated with interferon-gamma to elevate the baseline expression of MHC-I. RNA inhibition successfully blocked beta-2 microglubulin expression, thus preventing formation of functional MHC-I molecules