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- Title
Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes.
- Authors
Van Laake, L. W.; Van Donselaar, E. G.; Monshouwer-Kloots, J.; Schreurs, C.; Passier, R.; Humbel, B. M.; Doevendans, P. A.; Sonnenberg, A.; Verkleij, A. J.; Mummery, Christine L.
- Abstract
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.
- Subjects
EXTRACELLULAR matrix; EMBRYONIC stem cells; STEM cell transplantation; HEART cells; ELECTROPHYSIOLOGY
- Publication
Cellular & Molecular Life Sciences, 2010, Vol 67, Issue 2, p277
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-009-0179-z