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Making embryonic stem cells infarct‐avid
Author(s) -
Zhao Ming,
Barron Matthew R,
Li Zhixin,
Koprowski Stacy,
Lough John
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.33
Subject(s) - embryonic stem cell , microbiology and biotechnology , chemistry , induced pluripotent stem cell , in vitro , transplantation , biochemistry , biology , medicine , gene
A major factor limiting the engraftment of transplanted embryonic stem cells (ESCs) after myocardial infarction is the low rate of ESC retention within the infarcted site. Our objective is to improve the rate of engraftment by enabling transfused ESCs to recognize and bind infarcted tissues. Toward this end we have modified the membrane of ESCs with a positively‐charged ligand so that transfused cells are able to bind infarcted tissue by recognizing anionic phospholipids (APLDs) which are exposed in apoptotic and necrotic cells. METHODS. The C2A domain of Synaptotagmin I, which binds APLDs with high affinity and specificity, was covalently attached to the surface of mouse ESCs. The ability of C2A‐modified ESCs to remain pluripotent or differentiate was verified by immunohistochemistry using established molecular markers. Binding of C2A‐ESCs to dead and dying cardiomyocytes was verified in vitro. RESULTS. Under mild conjugation reaction conditions, C2A covalently attached to the ESC surface. ESC viability, pluripotency and ability to differentiate into cardiomyocytes were preserved after C2A modification. In culture, C2A‐ESCs avidly bound to dying, but not viable, cardiomyocytes. CONCLUSION. The binding of C2A‐ESCs to moribund cardiomyocytes demonstrates the concept that the retention rate of transplanted cells can be improved by conferring these cells with the ability to bind infarct tissues.