Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes.
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.
Heart Lung Center Utrecht, Utrecht, The Netherlands.
L W
LW
van Laake
E G
EG
van Donselaar
J
J
Monshouwer-Kloots
C
C
Schreurs
R
R
Passier
B M
BM
Humbel
P A
PA
Doevendans
A
A
Sonnenberg
A J
AJ
Verkleij
Christine L
CL
Mummery
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation*; D018919:Neovascularization, Physiologic