Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 67, Issue 2, Pages 277-290Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-009-0179-z
Keywords
Stem cells; Extracellular matrix; Cell transplantation; Myocardial infarction; Blood vessels
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Funding
- European Community [LSHM-CT-2005-018630]
- Dutch Platform for Tissue Engineering
- Interuniversity Cardiology Institute of the Netherlands
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Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for cardiac regeneration is hampered by the formation of fibrotic tissue around the grafts, preventing electrophysiological coupling. Investigating this process, we found that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and fibronectin, which they bind via appropriate integrins; (2) after transplantation into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and fibronectin; (3) integrin expression on hESC-CM largely matches the matrix type they encounter or secrete in vivo; (4) co-transplantation of hESC-derived endothelial cells and/or cardiac progenitors with hESC-CM results in the formation of functional capillaries; and (5) transplanted hESC-CM survive and mature in vivo for at least 24 weeks. These results form the basis of future developments aiming to reduce the adverse fibrotic reaction that currently complicates cell-based therapies for cardiac disease, and to provide an additional clue towards successful engraftment of cardiomyocytes by co-transplanting endothelial cells.
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