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Human pericytes for ischemic heart repair.

TitleHuman pericytes for ischemic heart repair.
Publication TypeJournal Article
Year of Publication2013
AuthorsChen C-W, Okada M, Proto JD, Gao X, Sekiya N, Beckman SA, Corselli M, Crisan M, Saparov A, Tobita K, Péault B, Huard J
JournalStem Cells
Volume31
Issue2
Pagination305-16
Date Published2013 Feb
ISSN1549-4918
KeywordsAnimals, Antigens, CD, Biological Markers, Cell Culture Techniques, Chemokine CCL2, Cyclooxygenase 2, Fibrosis, Gene Expression, Heme Oxygenase-1, Humans, Interleukin-6, Leukemia Inhibitory Factor, Membrane Proteins, Mice, Myocardial Infarction, Myocardium, Neovascularization, Physiologic, Pericytes, Proto-Oncogene Proteins c-sis, Regeneration, Transplantation, Heterologous, Vascular Endothelial Growth Factor A
Abstract

Human microvascular pericytes (CD146(+)/34(-)/45(-)/56(-)) 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 CD56+ 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-β, transforming growth factor-β1 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.

DOI10.1002/stem.1285
Alternate JournalStem Cells
PubMed ID23165704
PubMed Central IDPMC3572307
Grant ListG1000816 / / Medical Research Council / United Kingdom
P30 AG024827 / AG / NIA NIH HHS / United States
R01 AR049684 / AR / NIAMS NIH HHS / United States
R01AR49684 / AR / NIAMS NIH HHS / United States
R21 HL083057 / HL / NHLBI NIH HHS / United States
R21HL083057 / HL / NHLBI NIH HHS / United States