Human pericytes for ischemic heart repair

Chien Wen Chen, Masaho Okada, Jonathan D. Proto, Xueqin Gao, Naosumi Sekiya, Sarah A. Beckman, Mirko Corselli, Mihaela Crisan, Arman Saparov, Kimimasa Tobita, Bruno Peault, Johnny Huard

Research output: Contribution to journalArticlepeer-review

172 Citations (Scopus)

Abstract

Human microvascular pericytes (CD1461/342/452/562) contain multipotent precursors and repair/regenerate defective tissues, notably skeletal muscle. However, their ability to repair the ischemic heart remains unknown. We investigated the therapeutic potential of human pericytes, purified from skeletal muscle, for treating ischemic heart disease and mediating associated repair mechanisms in mice. Echocardiography revealed that pericyte transplantation attenuated left ventricular dilatation and significantly improved cardiac contractility, superior to CD561 myogenic progenitor transplantation, in acutely infarcted mouse hearts. Pericyte treatment substantially reduced myocardial fibrosis and significantly diminished infiltration of host inflammatory cells at the infarct site. Hypoxic pericyte-conditioned medium suppressed murine fibroblast proliferation and inhibited macrophage proliferation in vitro. High expression by pericytes of immunoregulatory molecules, including interleukin-6, leukemia inhibitory factor, cyclooxygenase-2, and heme oxygenase-1, was sustained under hypoxia, except for monocyte chemotactic protein-1. Host angiogenesis was significantly increased. Pericytes supported microvascular structures in vivo and formed capillary-like networks with/ without endothelial cells in three-dimensional cocultures. Under hypoxia, pericytes dramatically increased expression of vascular endothelial growth factor-A, platelet-derived growth factor-b, transforming growth factor-b1 and corresponding receptors while expression of basic fibroblast growth factor, hepatocyte growth factor, epidermal growth factor, and angiopoietin-1 was repressed. The capacity of pericytes to differentiate into and/or fuse with cardiac cells was revealed by green fluorescence protein labeling, although to a minor extent. In conclusion, intramyocardial transplantation of purified human pericytes promotes functional and structural recovery, attributable to multiple mechanisms involving paracrine effects and cellular interactions.

Original languageEnglish
Pages (from-to)305-316
Number of pages12
JournalStem Cells
Volume31
Issue number2
DOIs
Publication statusPublished - Feb 2013

Keywords

  • Angiogenesis
  • Immunomodulation
  • Myocardial infarction
  • Pericytes
  • Stem cell therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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