title: Restoration of angiogenic capacity of diabetes-insulted mesenchymal stem cells by oxytocin.
abstract: BACKGROUND
  Angiogenesis is the main therapeutic mechanism of cell therapy for cardiovascular diseases, but diabetes is reported to reduce the function and number of progenitor cells. Therefore, we studied the effect of streptozotocin-induced diabetes on the bone marrow-mesenchymal stem cell (MSC) function, and examined whether diabetes-impaired MSC could be rescued by pretreatment with oxytocin.
  
  
  RESULTS
  MSCs were isolated and cultured from diabetic (DM) or non-diabetic (non-DM) rat, and proliferation rate was compared. DM-MSC was pretreated with oxytocin and compared with non-DM-MSC. Angiogenic capacity was estimated by tube formation and Matrigel plug assay, and therapeutic efficacy was studied in rat myocardial infarction (MI) model.The proliferation and angiogenic activity of DM-MSC were severely impaired but significantly improved by pretreatment with oxytocin. Krüppel-like factor 2 (KLF2), a critical angiogenic factor, was dramatically reduced in DM-MSC and significantly restored by oxytocin. In the Matrigel plug assay, vessel formation of DM-BMSCs was attenuated but was recovered by oxytocin. In rat MI model, DM-MSC injection did not ameliorate cardiac injury, whereas oxytocin-pretreated DM-MSC improved cardiac function and reduced fibrosis.
  
  
  CONCLUSIONS
  Our results show that diabetes influenced MSC by reducing angiogenic capacity and therapeutic potential. We demonstrate the striking effect of oxytocin on stem cell dysfunction and suggest the use of oxytocin as a priming reagent in autologous stem cell therapy.
authors.affiliation: Heart Research Center, Chonnam National University Hospital, 42 Jebong-Ro, Dong-Gu, Gwangju 501-757, South Korea. cecilyk@chonnam.ac.kr.
authors.forename: Yong Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kwon
authors.forename: Moon Hwa
authors.initials: MH
authors.lastname: Hong
authors.forename: Wan Seok
authors.initials: WS
authors.lastname: Kang
authors.forename: Hye-yun
authors.initials: HY
authors.lastname: Jeong
authors.forename: Hye-jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Myung ho
authors.initials: Mh
authors.lastname: Jeong
authors.forename: Youngkeun
authors.initials: Y
authors.lastname: Ahn
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004338:Drug Combinations; D015870:Gene Expression; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000737:chemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010120:Oxytocics / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology*; D011509:Proteoglycans / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D013311:Streptozocin
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004338:Drug Combinations; C543921:Klf2 protein, rat; D051741:Kruppel-Like Transcription Factors; D007797:Laminin; D010120:Oxytocics; D011509:Proteoglycans; C059485:matrigel; D010121:Oxytocin; D013311:Streptozocin; D003094:Collagen
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