Embryonic Stem Cells: MHC Expression and Immunogenicity of Stem Cell-Derived Cellular Therapeutics pp. 165-198
Authors: (Gesine Fleischmann, Constança Figueiredo, Axel Seltsam, Rainer Blasczyk, Peter A. Horn, Institute for Transfusion Medicine, University Hospital Essen, Germany, and others)
Abstract: Embryonic stem cells (ESC) represent a theoretically inexhaustible source of precursor cells that can be differentiated into any cell type. These pluripotent, endlessly dividing cells have been hailed as a possible means for treating numerous diseases including degenerative, genetic or malignant diseases, or injury caused by trauma, infection, or inflammation. In addition, ESC are an invaluable research tool to study stem cell development and can serve as a platform to develop and test novel therapies. Beside the ethical limitations associated with the use of human embryonic stem cells, the application of cellular therapeutics derived from ESC is mainly hindered by two technical hurdles: The risk of tumor formation from undifferentiated ESC on the one hand and rejection of transplanted cells by the host‘s immune system on the other hand. The emergence of stem cell-based regenerative medicine as a potential therapy for substitution of organs and tissues is therefore intimately correlated with the necessity to inhibit the host immune response to the modified autologous or allogeneic stem cells. One of the most sought after goals in cell as well as tissue and organ transplantation is therefore the ability to induce specific immunologic tolerance to transplantation antigens since this would allow the replacement of host organs or tissues without the need for immunosuppression. In principle, this may be achieved by either altering properties of the host‘s immune system, achieving a state of specific tolerance (or ignorance), or alternatively by altering the properties of the transplanted cells and tissues, making these less immunogenic. Most desirable would be a stable, normal graft function in the complete absence of a requirement for maintenance of immunosuppression. Alternati-vely, the concept of employing tolerogenic strategies to permit graft acceptance with dramatically reduced immunosuppression requirements would already be a significant improvement.