Characterization of immunologic properties of murine and human embryonic stem cells and embryonic stem cell-derived cardiomyocytes

• Applicant: Dr. Tomo Saric
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2006 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 21316672

Since the initial derivation of human embryonic stem (ES) cells from the inner cell mass of a blastocyst the research toward potential therapeutic use of their differentiated derivatives has increased tremendously. Diseases that may be treatable with this new promising approach include, among others, neurodegenerative disorders such as Parkinson¿s disease, diabetes mellitus, myocardial infarction and liver failure. Recent experimental data suggest, for example, that ES cellderived cardiomyocytes could be used to functionally replace irreversibly lost cardiac cells in various animal models of heart disease. However, several obstacles have to be overcome before this new therapeutic modality becomes part of a standard clinical practice and, besides the risk of teratoma formation, the most formidable one is the immunological rejection of transplanted cells by histoincompatible recipients. Although the issue of graft rejection seems critical for the success of this therapeutic approach, the immunological properties of various somatic cells derived from ES cells, including cardiac cells, have not yet been explored. Therefore, it is the major objective of this proposal to characterize the antigenic and immunogenic properties of murine and human ES cell-derived cardiomyocytes, which will be used as a model for ES cell-derived mature cells with a therapeutic relevance. To this end we will: a) determine the expression of major histocompatibility complex class I and II molecules in different ES cell-derived cardiac subtypes (pacemaker, atrial and ventricular cells) and their inducibility by inflammatory cytokines, b) assess in vitro the susceptibility to lysis by activated cytotoxic T cells and NK cells of ES cells at different stages of differentiation and ES cell-derived cardiomyocytes, and c) to determine the engraftment capacity and immunogenic properties of murine ES cell-derived cardiomyocytes upon transplantation into syngeneic, allogeneic or immunodeficient mice. These studies will improve our understanding of the immunologic properties of ES-cell derived cardiac cells and will help design rational strategies for preventing their rejection, if it occurs.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1109: Embryonal and Tissue-Specific Stem Cells - Regenerative Systems for Cell and Tissue Repair
• Participating Person: Professor Dr. Jürgen Hescheler