Abstract 15793: N-Cadherin Overexpression in Adipocyte Derived Mesenchymal Stem Cells Enhances Its Cardioprotective Effects

• Published in: Circulation (New York, N.Y.) Vol. 138; no. Suppl_1 Suppl 1; p. A15793
• Main Authors: Yan, Wenjun, Gan, Lu, Xia, Yunlong, Guo, Yongzhen, Lau, Wayne B, Gao, Erhe, Christopher, Theodore, Lopez, Bernard, Koch, Walter, Wang, Yajing, Ma, Xinliang, Tao, Ling
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 06-11-2018
• ISSN: 0009-7322; 1524-4539

IntroductionToxic microenvironment restricted the engrafted mesenchymal stem cells survival and reparative effects on ischemic heart failure (IHF). We recently reported that CTRP9 improves adipose tissue derived mesenchymal stem cells (AT-MSCs) cardioprotective function by binding to N-Cadherin.HypothesisCurrent study further investigated whether N-Cadherin overexpression in AT-MSCs may enhance their cardioprotective capability against IHF.MethodsAT-MSCs were isolated from C57BL/6J mice. Passage 3 AT-MSCs were transfected with adenovirus harboring N-cadherin (AT-MSC-Ncad) or control adenovirus (AT-MSC-Con) and stained with 5μM CM-DiI (a celltracker) before transplantation. C57BL/6J mice were subjected to sham MI or MI. Immediately after coronary occlusion, MI animals were randomized to receive PBS, AT-MSC-Con (2х10 passage 3 cells were directly injected into the infarct border zone) or AT-MSC-Ncad. Cardiac function was assessed by echocardiography 1 and 4 weeks after sham MI or MI. AT-MSCs survival, capillary density, and fibrosis were determined by histological analysis (CM-DiI, CD31, and masson-trichrome staining) at the end of experiments.ResultsAdenovirus harboring N-cadherin transfection increased N-cadherin protein expression over 40-fold in AT-MSCs. Compared with AT-MSC-Con, MI+AT-MSC-Ncad significantly improved LVEF (39.50±4.20% in MI+AT-MSC-Ncad group vs. 26.24±4.18% in MI+AT-MSC-Con group; P <0.01) 4 weeks after MI. Histological analysis showed that N-cadherin overexpression dramatically increased engrafted AT-MSC survival/retention 1 day, 3 days, and 7 days after MI (all P <0.05). Moreover, AT-MSC-Ncad significantly increased capillary density and reduced fibrosis. In vitro experiments utilizing xCELLigence system demonstrated that N-cadherin overexpression significantly increased the adhesive capacity of AT-MSCs compared with control (P <0.01). Finally, we observed that CTRP9 treatment in addition to N-cadherin overexpression (CTRP9+N-cad) significantly increased FGF2, HGF, PDGFA and VEGFA expression and secretion compared to CTRP9+Con (all P <0.05 vs. CTRP9+Con).ConclusionsWe demonstrate that N-cadherin overexpression enhances the protective effects of MSCs on ischemic heart injury. The beneficial role of N-cadherin overexpression may be linked to its effects upon the adhesive capacity and paracrine function of MSCs.