A major factor limiting the engraftment of transplanted stem cells after myocardial infarction is the low rate of retention in the infarcted site. Our long-term objective is to improve engraftment by enabling stem cells to recognize and bind infarcted tissue. To this end, we proposed to modify the surface of embryonic stem cells (ESCs) with the C2A domain of synaptotagmin I; this allows the engineered stem cells to bind to dead and dying cardiac cells by recognizing phosphatidylserine (PS). The latter is a molecular marker for apoptotic and necrotic cells. The C2A domain of synaptotagmin I, which binds PS with high affinity and specificity, was attached to the surface of mouse ESCs using the biotin-avidin coupling mechanism. Binding of C2A-ESCs to dead and dying cardiomyocytes was tested in vitro. After the surface modification, cellular physiology was examined for viability, pluripotency, and differentiation potential. C2A covalently attached to the ESC surface at an average of about 1 million C2A molecules per cell under mild conjugation reaction conditions. C2A-ESCs avidly bound to dying, but not viable, cardiomyocytes in culture. The normal physiology of C2A-modified ESCs was maintained. The binding of C2A-ESCs to moribund cardiomyocytes demonstrates that the retention of transplanted cells may be improved by conferring these cells with the ability to bind infarcted tissue. Once established, this novel approach may be applicable to other types of transplanted therapeutic cells.
No Supplementary Data.
Acute myocardial infarction;
C2A domain of synaptotagmin I;
Document Type: Research Article
Publication date: 2010-02-01
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Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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