title: Trimetazidine protects umbilical cord mesenchymal stem cells against hypoxia and serum deprivation induced apoptosis by activation of Akt.
abstract: BACKGROUND
  Mesenchymal stem cell (MSC) transplantation is a promising therapy for cardiac repair. However, the efficacy is limited by the poor viability of MSCs in the infarcted heart. Recent findings have implicated that trimetazidine (TMZ) enhanced the survival of the stem cells under various conditions. However, as the stem cells in these studies were animal-derived, little information is available about the effects of TMZ on human MSCs. Herein, we propose that TMZ may protect human MSCs against apoptosis induced by Hypoxia/Serum deprivation (H/SD).
  
  
  METHODS
  Human umbilical cord MSCs (UC-MSCs) from Wharton's jelly were pretreated with 10µM TMZ of H/SD with or without the Akt inhibitor LY294002. The morphological changes were assessed using Hoechst 33342. Apoptosis was evaluated via Annexin V/PI staining; and apoptosis-related proteins were detected using Western-blot. Protein chip technology was used to screen for differences between the cell supernatants.
  
  
  RESULTS
  TMZ had a significant protective effect against H/SD-induced apoptosis, accompanied by an increase in Bcl-2 and p-Akt. The TMZ-mediated anti-apoptotic effect on MSCs could be attenuated by treatment with LY294002. Moreover, protein chip assays showed that TMZ treatment increased the paracrine functions of MSCs.
  
  
  CONCLUSIONS
  Trimetazidine protects human UC-MSCs from H/SD-induced apoptosis via the Akt pathway and may therefore be a potentially useful therapeutic adjunct for transplanting MSCs into damaged heart after myocardial infarction.
authors.affiliation: Emergency and Critical Center, Department of Cardiovascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Xuhe
authors.initials: X
authors.lastname: Gong
authors.forename: Guangpu
authors.initials: G
authors.lastname: Fan
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Guogan
authors.initials: G
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D016895:Culture Media, Serum-Free; D018507:Gene Expression Regulation, Developmental; D019254:Genes, bcl-2; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000473:pathology; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D014292:Trimetazidine / Q000008:administration & dosage*; D014470:Umbilical Cord / Q000187:drug effects* / Q000473:pathology
chemical_list: D016895:Culture Media, Serum-Free; D051057:Proto-Oncogene Proteins c-akt; D014292:Trimetazidine