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: Research - peer-reviewArticle

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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.

LanguageEnglish
Pages305-316
Number of pages12
JournalStem Cells
Volume31
Issue number2
DOIs
StatePublished - Feb 2013
Externally publishedYes

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Pericytes
Transplantation
Skeletal Muscle
Hypoxia
Angiopoietin-1
Leukemia Inhibitory Factor
Heme Oxygenase-1
Hepatocyte Growth Factor
Chemokine CCL2
Platelet-Derived Growth Factor
Transforming Growth Factors
Fibroblast Growth Factor 2
Cyclooxygenase 2
Conditioned Culture Medium
Coculture Techniques
Epidermal Growth Factor
Vascular Endothelial Growth Factor A
Myocardial Ischemia
Echocardiography
Dilatation

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Chen, C. W., Okada, M., Proto, J. D., Gao, X., Sekiya, N., Beckman, S. A., ... Huard, J. (2013). Human pericytes for ischemic heart repair. Stem Cells, 31(2), 305-316. DOI: 10.1002/stem.1285

Human pericytes for ischemic heart repair. / Chen, Chien Wen; Okada, Masaho; Proto, Jonathan D.; Gao, Xueqin; Sekiya, Naosumi; Beckman, Sarah A.; Corselli, Mirko; Crisan, Mihaela; Saparov, Arman; Tobita, Kimimasa; Peault, Bruno; Huard, Johnny.

In: Stem Cells, Vol. 31, No. 2, 02.2013, p. 305-316.

Research output: Research - peer-reviewArticle

Chen, CW, Okada, M, Proto, JD, Gao, X, Sekiya, N, Beckman, SA, Corselli, M, Crisan, M, Saparov, A, Tobita, K, Peault, B & Huard, J 2013, 'Human pericytes for ischemic heart repair' Stem Cells, vol 31, no. 2, pp. 305-316. DOI: 10.1002/stem.1285
Chen CW, Okada M, Proto JD, Gao X, Sekiya N, Beckman SA et al. Human pericytes for ischemic heart repair. Stem Cells. 2013 Feb;31(2):305-316. Available from, DOI: 10.1002/stem.1285
Chen, Chien Wen ; Okada, Masaho ; Proto, Jonathan D. ; Gao, Xueqin ; Sekiya, Naosumi ; Beckman, Sarah A. ; Corselli, Mirko ; Crisan, Mihaela ; Saparov, Arman ; Tobita, Kimimasa ; Peault, Bruno ; Huard, Johnny. / Human pericytes for ischemic heart repair. In: Stem Cells. 2013 ; Vol. 31, No. 2. pp. 305-316
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