Paracrine effect of Wnt11-overexpressing mesenchymal stem cells on ischemic injury Journal Article


Authors: Zuo, S.; Jones, W. K.; Li, H; He, Z.; Pasha, Z.; Yang, Y; Wang, Y; Fan, G. C.; Ashraf, M.; Xu, M
Article Title: Paracrine effect of Wnt11-overexpressing mesenchymal stem cells on ischemic injury
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-beta2 (TGFbeta2) (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 TGFbeta2 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.
Journal Title: Stem cells and development
Volume: 21
Issue: 4
ISSN: 1557-8534; 1547-3287
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: 598
End Page: 608
Language: eng
DOI/URL:
Notes: LR: 20131018; GR: HL081859/HL/NHLBI NIH HHS/United States; GR: HL083236/HL/NHLBI NIH HHS/United States; GR: HL087246/HL/NHLBI NIH HHS/United States; GR: HL087861/HL/NHLBI NIH HHS/United States; GR: HL105176/HL/NHLBI NIH HHS/United States; GR: R01 HL081859-05/HL/NHLBI NIH HHS/United States; GR: R01 HL083236-05/HL/NHLBI NIH HHS/United States; GR: R01 HL087246-04/HL/NHLBI NIH HHS/United States; GR: R01 HL087861/HL/NHLBI NIH HHS/United States; GR: R01 HL087861-05/HL/NHLBI NIH HHS/United States; GR: R01 HL105176-01/HL/NHLBI NIH HHS/United States; GR: R01 HL110740/HL/NHLBI NIH HHS/United States; JID: 101197107; 0 (Transforming Growth Factor beta2); 0 (Wnt Proteins); 0 (Wnt11 protein, rat); NIHMS290363; OID: NLM: NIHMS290363; OID: NLM: PMC3156900; 2011/06/01 [aheadofprint]; ppublish