Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes |
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Authors: | L W van Laake E G van Donselaar J Monshouwer-Kloots C Schreurs R Passier B M Humbel P A Doevendans A Sonnenberg A J Verkleij Christine L Mummery |
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Institution: | (1) Heart Lung Center Utrecht, Utrecht, The Netherlands;(2) Cellular Architecture and Dynamics, Faculty of Sciences, Utrecht University, Utrecht, The Netherlands;(3) Department of Anatomy and Embryology, Leiden University Medical Center, Postal zone: S-1-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands;(4) The Netherlands Cancer Institute, Amsterdam, The Netherlands |
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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. |
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