Paracrine effect of wnt11-overexpressing mesenchymal stem cells on ischemic injury

Shi Zuo, W. Keith Jones, Hongxia Li, Zhisong He, Zeeshan Pasha, Yueting Yang, Yigang Wang, Guo Chang Fan, Muhammad Ashraf, Meifeng Xu

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Our previous studies have suggested that transduction of Wnt11 directly increases bone marrow-derived mesenchymal stem cells (MSCs) differentiation into cardiac phenotypes. In this study, we investigated whether Wnt11 enhances MSC-mediated cardioprotection via paracrine fashion after acute ischemia. MSCs were harvested from male rat bone marrow and transduced with Wnt11 (MSC Wnt11). An acute myocardial infarction model in rats was developed by ligation of the left anterior descending coronary artery. MSC Wnt11 were transplanted into the peri-infarct region after acute myocardial infarction. To mimic ischemic injury, cultured cardiomyocytes (CMs) isolated from neonatal ventricles were exposed to hypoxia. ELISA studies indicated that the release of Wnt11 (3.45-fold) as well as transforming growth factor-β2 (TGFβ2) (1.5-fold) was significantly increased from MSC Wnt11 compared with transduced control MSC (MSC Null). Hypoxia-induced apoptosis and cell death was significantly reduced when CM were co-cultured with MSC Wnt11 in a dual chamber system. The cell protection mediated by MSC Wnt11 was mimicked by treating CM with conditioned medium obtained from MSC Wnt11 and abrogated by Wnt11- and TGFβ2 neutralizing antibodies. Further, animals receiving MSC Wnt11 showed a significant improvement in cardiac contractile function as assessed by echocardiography. Masson trichrome and TUNEL staining showed a significant reduction in infarct size and apoptosis of CM in MSC Wnt11-treated animals. Transplantation of MSC Wnt11 improved cardiac function. The release of Wnt11 and other factors from transplanted MSC Wnt11 is more likely responsible for protection of native CM at risk.

Original languageEnglish (US)
Pages (from-to)598-608
Number of pages11
JournalStem Cells and Development
Volume21
Issue number4
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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    Zuo, S., Jones, W. K., Li, H., He, Z., Pasha, Z., Yang, Y., Wang, Y., Fan, G. C., Ashraf, M., & Xu, M. (2012). Paracrine effect of wnt11-overexpressing mesenchymal stem cells on ischemic injury. Stem Cells and Development, 21(4), 598-608. https://doi.org/10.1089/scd.2011.0071