Transduction of Wnt11 promotes mesenchymal stem cell transdifferentiation into cardiac phenotypes

Zhisong He, Hongxia Li, Shi Zuo, Zeeshan Pasha, Yigang Wang, Yueting Yang, Wenping Jiang, Muhammad Ashraf, Meifeng Xu

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Transplantation of mesenchymal stem cells (MSCs) has emerged as a potential treatment for ischemic heart repair. Previous studies have suggested that Wnt11 plays a critical role in cardiac specification and morphogenesis. In this study, we examined whether transduction of Wnt11 directly increases MSC differentiation into cardiac phenotypes. MSCs harvested from rat bone marrow were transduced with both Wnt11 and green fluorescent protein (GFP) (MSC Wnt11) using the murine stem cell virus (pMSCV) retroviral expression system; control cells were only GFP-transfected (MSC Null). Compared with control cells, MSC Wnt11 was shown to have higher expression of Wnt11 by immunofluorescence, real-time polymerase chain reaction, and western blotting. MSC Wnt11 shows a higher expression of cardiac-specific genes, including GATA-4, brain natriuretic peptide (BNP), islet-1, and α-actinin, after being cultured with cardiomyocytes (CMs) isolated from ventricles of neonatal (1-3 day) SD rats. Some MSC Wnt11 were positive for α-actinin when MSCs were cocultured with native CMs for 7 days. Electron microscopy further confirmed the appearance of sarcomeres in MSC Wnt11. Connexin 43 was found between GFP-positive MSCs and neonatal rat CMs labeled with red fluorescent probe PKH26. The transdifferentiation rate was significantly higher in MSC Wnt11 than in MSC Null, as assessed by flow cytometery. Functional studies indicated that the differentiation of MSC Wnt11 was diminished by knockdown of GATA-4 with GATA-4-siRNA. Transduction of Wnt11 into MSCs increases their differentiation into CMs by upregulating GATA-4.

Original languageEnglish (US)
Pages (from-to)1771-1778
Number of pages8
JournalStem Cells and Development
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2011

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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