Aims: The application of autologous endothelial progenitor cells (EPC) is a promising approach in cardiovascular regeneration, but the availability of cells in appropriate numbers is the limiting factor. Allogeneic EPC would be an alternative, and we therefore analysed the immunogenicity of EPC-derived endothelial cells (EC) to evaluate their potential usefulness.
Methods and results: Circulating EPC from rat were differentiated into EC and characterized phenotypically and functionally. Major histocompatibility complex (MHC) expression in response to interferon-gamma was determined compared with rat aortic EC, and in vitro humoral and cellular allogeneic responses were analysed. To determine the in vivo effects, acellular aortic grafts were endothelialized in vitro with EPC-derived EC and transplanted in a complete allogeneic mismatch rat aortic interposition model. EPC-derived EC expressed endothelial-specific markers and low levels of MHC class I (MHC I), but no constitutive MHC class II (MHC II). When stimulated with interferon-gamma, they upregulated MHC I and moderately upregulated MHC II. They were protected against alloantibody/complement-mediated lysis and allospecific cytotoxic T lymphocyte activity. They were less potent in allogeneic stimulation of CD4 T cells than aortic EC. Seeding of EPC-derived EC into acellular grafts led to excellent endothelialization, and allogeneic aortic transplantation induced only mild inflammatory responses without signs of rejection.
Conclusion: EPC-derived EC are protected against allospecific cellular immune responses and humoral-mediated attacks in vitro. When transplanted in vivo as a component of vascular grafts, these cells are not rejected, which makes them useful in therapeutic applications, especially vascular reconstruction.