title: Lentivirus-mediated Wnt11 gene transfer enhances Cardiomyogenic differentiation of skeletal muscle-derived stem cells.
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.
authors.affiliation: Stem Cell Research Center, Children's Hospital of Pittsburgh and Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Xiang
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Naosumi
authors.initials: N
authors.lastname: Sekiya
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Mu
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.forename: Chien-Wen
authors.initials: CW
authors.lastname: Chen
authors.forename: Masaho
authors.initials: M
authors.lastname: Okada
authors.forename: James
authors.initials: J
authors.lastname: Cummins
authors.forename: Burhan
authors.initials: B
authors.lastname: Gharaibeh
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics*; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D018485:Muscle Fibers, Skeletal / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; C508957:Wnt11 protein, mouse