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Lentivirus-mediated wnt11 gene transfer enhances cardiomyogenic differentiation of skeletal muscle-derived stem cells

Xiang, G and Yang, Q and Wang, B and Sekiya, N and Mu, X and Tang, Y and Chen, CW and Okada, M and Cummins, J and Gharaibeh, B and Huard, J (2011) Lentivirus-mediated wnt11 gene transfer enhances cardiomyogenic differentiation of skeletal muscle-derived stem cells. Molecular Therapy, 19 (4). 790 - 796. ISSN 1525-0016

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Abstract

Wnt signaling plays a crucial role in regulating cell proliferation, differentiation and inducing cardiomyogenesis. Skeletal muscle-derived stem cells (MDSCs) have been shown to be multipotent; however, their potential to aid in the healing of the heart after myocardial infarction appears to be due to the paracrine effects they impart on the host environment. The goal of this study was to investigate whether Wnt11 could promote the differentiation of MDSCs into cardiomyocytes and enhance the repair of infarcted myocardium. MDSCs transduced with a lentivirus encoding for Wnt11 increased mRNA and protein expression of the early cardiac markers NK2 transcription factor related 5 (NKx2.5) and Connexin43 (Cx43) and also led to an increased expression of late-stage cardiac markers including: α, Β-myosin heavy chain (MHC) and brain natriuretic protein (BNP) at the mRNA level, and MHC and Troponin I (TnI) at the protein level. We also observed that Wnt11 expression significantly enhanced c-jun N-terminal kinase activity in transduced MDSCs, and that some of the cells beat spontaneously but are not fully differentiated cardiomyocytes. Finally, lentivirus-Wnt11-transduced MDSCs showed greater survival and cardiac differentiation after being transplanted into acutely infarct-injured myocardium. These findings could one day lead to strategies that could be utilized in cardiomyoplasty treatments of myocardial infarction. © The American Society of Gene & Cell Therapy.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Xiang, G
Yang, Q
Wang, Bbingwang@pitt.eduBINGWANG
Sekiya, N
Mu, X
Tang, Yyit3@pitt.eduYIT3
Chen, CW
Okada, M
Cummins, J
Gharaibeh, Bburhan@pitt.eduBURHAN0000-0002-5947-1232
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 1 January 2011
Date Type: Publication
Journal or Publication Title: Molecular Therapy
Volume: 19
Number: 4
Page Range: 790 - 796
DOI or Unique Handle: 10.1038/mt.2011.5
Schools and Programs: School of Medicine > Orthopaedic Surgery
Refereed: Yes
ISSN: 1525-0016
MeSH Headings: Animals; Blotting, Western; Cell Differentiation--genetics; Cell Differentiation--physiology; Genetic Vectors--genetics; Immunohistochemistry; Lentivirus--genetics; Male; Mice; Mice, SCID; Muscle Fibers, Skeletal--cytology; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells--cytology; Stem Cells--metabolism; Wnt Proteins--genetics; Wnt Proteins--metabolism
Other ID: NLM PMC3070113
PubMed Central ID: PMC3070113
PubMed ID: 21304494
Date Deposited: 04 Apr 2014 15:57
Last Modified: 02 Feb 2019 16:56
URI: http://d-scholarship.pitt.edu/id/eprint/20886

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