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Human skeletal muscle cells with a slow adhesion rate after isolation and an enhanced stress resistance improve function of ischemic hearts

Okada, M and Payne, TR and Drowley, L and Jankowski, RJ and Momoi, N and Beckman, S and Chen, WCW and Keller, BB and Tobita, K and Huard, J (2012) Human skeletal muscle cells with a slow adhesion rate after isolation and an enhanced stress resistance improve function of ischemic hearts. Molecular Therapy, 20 (1). 138 - 145. ISSN 1525-0016

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Identification of cells that are endowed with maximum potency could be critical for the clinical success of cell-based therapies. We investigated whether cells with an enhanced efficacy for cardiac cell therapy could be enriched from adult human skeletal muscle on the basis of their adhesion properties to tissue culture flasks following tissue dissociation. Cells that adhered slowly displayed greater myogenic purity and more readily differentiated into myotubes in vitro than rapidly adhering cells (RACs). The slowly adhering cell (SAC) population also survived better than the RAC population in kinetic in vitro assays that simulate conditions of oxidative and inflammatory stress. When evaluated for the treatment of a myocardial infarction (MI), intramyocardial injection of the SACs more effectively improved echocardiographic indexes of left ventricular (LV) remodeling and contractility than the transplantation of the RACs. Immunohistological analysis revealed that hearts injected with SACs displayed a reduction in myocardial fibrosis and an increase in infarct vascularization, donor cell proliferation, and endogenous cardiomyocyte survival and proliferation in comparison with the RAC-treated hearts. In conclusion, these results suggest that adult human skeletal muscle-derived cells are inherently heterogeneous with regard to their efficacy for enhancing cardiac function after cardiac implantation, with SACs outperforming RACs. © The American Society of Gene & Cell Therapy.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Okada, M
Payne, TR
Drowley, L
Jankowski, RJ
Momoi, N
Beckman, S
Chen, WCW
Keller, BB
Tobita, Kkit3@pitt.eduKIT3
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 1 January 2012
Date Type: Publication
Journal or Publication Title: Molecular Therapy
Volume: 20
Number: 1
Page Range: 138 - 145
DOI or Unique Handle: 10.1038/mt.2011.229
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
School of Medicine > Orthopaedic Surgery
School of Medicine > Pediatrics
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 1525-0016
MeSH Headings: Adolescent; Aged; Animals; Apoptosis--genetics; Cell Adhesion; Cell Differentiation; Cell Proliferation; Cell Survival--genetics; Cicatrix--pathology; Gene Expression Profiling; Humans; Immunophenotyping; Intercellular Signaling Peptides and Proteins--genetics; Intercellular Signaling Peptides and Proteins--metabolism; Male; Mice; Mice, Inbred NOD; Mice, SCID; Middle Aged; Muscle Fibers, Skeletal--cytology; Muscle Fibers, Skeletal--metabolism; Muscle Fibers, Skeletal--transplantation; Myocardial Ischemia--metabolism; Myocardial Ischemia--therapy; Myocardium--metabolism; Myocardium--pathology; Myocytes, Cardiac--metabolism; Myocytes, Cardiac--pathology; Neovascularization, Physiologic; Oxidative Stress; Stress, Physiological
Other ID: NLM PMC3255579
PubMed Central ID: PMC3255579
PubMed ID: 22068427
Date Deposited: 04 Apr 2014 15:47
Last Modified: 03 Feb 2019 01:55


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