Abstracts (complete list) - Wissenschaft Online

Lukas Frenzel, Zeinab Abdullah, Anja Kriegeskorte, Rebecca Borsutzky, Manoj K.
Gupta, Olaf Utermöhlen, Dirk H. Busch, Martin Krönke, Jürgen Hescheler, Tomo Saric
Immunological properties of murine embryonic stem cellderived
cardiomyocytes
Embryonic stem (ES) cells are regarded as a very promising source of differentiated
cells for tissue regeneration. ES cell-derived cardiomyocytes could functionally replace
irreversibly lost cardiac tissue in various animal models of ischaemic heart disease.
However, clinical application of this therapeutic approach will be hampered by
immunological rejection of transplanted cells by histoincompatible recipients. To address
the question of immunological properties of murine ES cell-derived cardiomyocytes we
have utilized a transgenic murine ES cell line D3aPIG engineered to express GFP and
antibiotic resistance specifically in ES cell-derived heart cells. This cell line enabled us to
highly purify GFP-positive cardiac progenitor cells and to specifically address the
question of their immunogenic properties. To this end, we have determined their
immunophenotype by flow cytometry, assessed their response to the inflammatory
cytokine interferon gamma, assayed their physical interaction with cytotoxic T
lymphocytes (CTLs) and tested their susceptibility to lysis by activated NK cells and
cytotoxic T cells. These studies have demonstrated that ES cell-derived cardiomyocytes
constitutively express very low levels of MHC class I molecules on their cell surface,
which were strongly upregulated by interferon gamma. Interestingly, the cytotoxicity
experiments revealed that ES cell-derived cardiac cells were resistant to killing by poly I:
C activated syngeneic and allogeneic NK cells as well as by allogeneic cytotoxic T cells.
Even strong upregulation of MHC class I molecules on the surface of cardiac cells by
interferon gamma did not render them sensitive to lysis by immune effector cells,
indicating that transplanted ES cell-derived cardiomyocytes might be less susceptible to
rejection as compared to whole organ transplants. Further studies are planned to
elucidate the molecular basis of this resistance and to assess the engraftment capacity
and immunogenicity of ES cell-derived cardiomyocytes in vivo upon allotransplantation.