Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes

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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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.

Original languageEnglish
Pages (from-to)277-290
Number of pages14
JournalCellular and Molecular Life Sciences
Volume67
Issue number2
DOIs
Publication statusPublished - 1 Jan 2010
Externally publishedYes

Keywords

  • Blood vessels
  • Cell transplantation
  • Extracellular matrix
  • Myocardial infarction
  • Stem cells

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  • Cite this

    Van Laake, L. W., Van Donselaar, E. G., Monshouwer-Kloots, J., Schreurs, C., Passier, R., Humbel, B. M., ... Mummery, C. L. (2010). Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes. Cellular and Molecular Life Sciences, 67(2), 277-290. https://doi.org/10.1007/s00018-009-0179-z