Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction

Thomas P. Kraehenbuehl, Lino S. Ferreira, Alison M. Hayward, Matthias Nahrendorf, André J. van der Vlies, Eliza Vasile, Ralph Weissleder, Robert Langer, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

We present use of a synthetic, injectable matrix metalloproteinase (MMP)- responsive, bioactive hydrogel as an in situ forming scaffold to deliver thymosin β4 (Tβ4), a pro-angiogenic and pro-survival factor, along with vascular cells derived from human embryonic stem cells (hESC) in ischemic injuries to the heart in a rat model. The gel was found to substitute the degrading extracellular matrix in the infarcted myocardium of rats and to promote structural organization of native endothelial cells, while some of the delivered hESC-derived vascular cells formed de novo capillaries in the infarct zone. Magnetic resonance imaging (MRI) revealed that the microvascular grafts effectively preserved contractile performance 3 d and 6 wk after myocardial infarction, attenuated left ventricular dilation, and decreased infarct size as compared to infarcted rats treated with PBS injection as a control (3 d ejection fraction, + ∼7%, P < 0.001; 6 wk ejection faction, + ∼12%, P < 0.001). Elevation in vessel density was observed in response to treatment, which may be due in part to elevations in human (donor)-derived cytokines EGF, VEGF and HGF (1 d). Thus, a clinically relevant matrix for dual delivery of vascular cells and drugs may be useful in engineering sustained tissue preservation and potentially regenerating ischemic cardiac tissue.

Original languageEnglish (US)
Pages (from-to)1102-1109
Number of pages8
JournalBiomaterials
Volume32
Issue number4
DOIs
StatePublished - Feb 2011

Keywords

  • Biomimetic material
  • Cardiac tissue engineering
  • Hydrogel
  • Matrix metalloproteinase
  • Stem cell
  • Vascular grafts

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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    Kraehenbuehl, T. P., Ferreira, L. S., Hayward, A. M., Nahrendorf, M., van der Vlies, A. J., Vasile, E., Weissleder, R., Langer, R., & Hubbell, J. A. (2011). Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction. Biomaterials, 32(4), 1102-1109. https://doi.org/10.1016/j.biomaterials.2010.10.005