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Human pericytes for ischemic heart repair

Chen, CW and Okada, M and Proto, JD and Gao, X and Sekiya, N and Beckman, SA and Corselli, M and Crisan, M and Saparov, A and Tobita, K and Peault, B and Huard, J (2013) Human pericytes for ischemic heart repair. Stem Cells, 31 (2). 305 - 316. ISSN 1066-5099

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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. © 2012 AlphaMed Press.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Chen, CW
Okada, M
Proto, JD
Gao, X
Sekiya, N
Beckman, SA
Corselli, M
Crisan, M
Saparov, A
Tobita, Kkit3@pitt.eduKIT3
Peault, B
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 1 February 2013
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: Stem Cells
Volume: 31
Number: 2
Page Range: 305 - 316
DOI or Unique Handle: 10.1002/stem.1285
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Developmental Biology
School of Medicine > Orthopaedic Surgery
School of Medicine > Pathology
School of Medicine > Pediatrics
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 1066-5099
PubMed ID: 23165704
Date Deposited: 31 Mar 2014 14:52
Last Modified: 02 Feb 2019 21:55
URI: http://d-scholarship.pitt.edu/id/eprint/20801

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