title: Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation.
abstract: OBJECTIVE
  Mesenchymal stem cell (MSC) transplantation is a promising therapy for ischemic heart diseases. However, poor cell survival after transplantation greatly limits the therapeutic efficacy of MSCs. The purpose of this study was to investigate the protective effect of angiopoietin-1 (Ang1) preconditioning on MSC survival and subsequent heart function improvement after transplantation.
  
  
  METHODS
  MSCs were cultured with or without 50 ng/ml Ang1 in complete medium for 24 h prior to experiments on cell survival and transplantation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Hoechst staining were applied to evaluate MSC survival after serum deprivation in vitro, while cell survival in vivo was detected by terminal deoxynucleotidyl transferase biotin-dUPT nick end labeling (TUNEL) assay 24 and 72 h after transplantation. Heart function and infarct size were measured four weeks later by small animal echocardiography and Masson's trichrome staining, respectively.
  
  
  RESULTS
  Ang1 preconditioning induced Akt phosphorylation and increased expression of Bcl-2 and the ratio of Bcl-2/Bax. In comparison with non-preconditioned MSCs, Ang1-preconditioned cell survival was significantly increased while the apoptotic rate decreased in vitro. However, the PI3K/Akt pathway inhibitor, LY294002, abrogated the protective effect of Ang1 preconditioning. After transplantation, the Ang1-preconditioned-MSC group showed a lower death rate, smaller infarct size, and better heart functional recovery compared to the non-preconditioned-MSC group.
  
  
  CONCLUSIONS
  Ang1 preconditioning enhances MSC survival, contributing to further improvement of heart function.
authors: Cardiovascular Key Lab of Zhejiang Province, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors: Xian-bao
authors: XB
authors: Liu
authors: Han
authors: H
authors: Chen
authors: Hui-qiang
authors: HQ
authors: Chen
authors: Mei-fei
authors: MF
authors: Zhu
authors: Xin-yang
authors: XY
authors: Hu
authors: Ya-ping
authors: YP
authors: Wang
authors: Zhi
authors: Z
authors: Jiang
authors: Yin-chuan
authors: YC
authors: Xu
authors: Mei-xiang
authors: MX
authors: Xiang
authors: Jian-an
authors: JA
authors: Wang
mesh_terms: D042683:Angiopoietin-1 / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002867:Chromones / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D004452:Echocardiography / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009025:Morpholines / Q000494:pharmacology; D009203:Myocardial Infarction / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D042683:Angiopoietin-1; D002867:Chromones; D003470:Culture Media; D004791:Enzyme Inhibitors; D009025:Morpholines; D013778:Tetrazolium Salts; D013844:Thiazoles; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C022616:thiazolyl blue