Composite scaffold provides a cell delivery platform for cardiovascular repair

Amandine F.G. Godier-Furnémont, Timothy P. Martens, Michael S. Koeckert, Leo Wan, Jonathan Parks, Kotaro Arai, Geping Zhang, Barry Hudson, Shunichi Homma, Gordana Vunjak-Novakovic

Research output: Contribution to journalArticle

194 Scopus citations

Abstract

Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-β promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair.

Original languageEnglish (US)
Pages (from-to)7974-7979
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number19
DOIs
StatePublished - May 10 2011
Externally publishedYes

Keywords

  • Biomaterial
  • Cardiac patch
  • Cardiac repair
  • Human stem cell

ASJC Scopus subject areas

  • General

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  • Cite this

    Godier-Furnémont, A. F. G., Martens, T. P., Koeckert, M. S., Wan, L., Parks, J., Arai, K., Zhang, G., Hudson, B., Homma, S., & Vunjak-Novakovic, G. (2011). Composite scaffold provides a cell delivery platform for cardiovascular repair. Proceedings of the National Academy of Sciences of the United States of America, 108(19), 7974-7979. https://doi.org/10.1073/pnas.1104619108