title: Mesenchymal stem cells overexpressing GCP-2 improve heart function through enhanced angiogenic properties in a myocardial infarction model.
abstract: OBJECTIVE
  In this study, our aim was to evaluate the angio-vasculogenic properties of human adipose tissue-derived mesenchymal stem cells overexpressing the granulocyte chemotactic protein (GCP)-2 (hASCs/GCP-2) and to determine possible therapeutic effects in an experimental ischaemic heart model.
  
  
  RESULTS
  Quantitative real-time (qRT)-PCR results revealed that hASCs/GCP-2 expressed significantly higher levels of pro-angiogenic genes, including vascular endothelial growth factor (VEGF)-A, hepatocyte growth factor (HGF), and interleukin (IL)-8, when compared with control-vector transduced hASCs or human umbilical vascular endothelial cells (HUVECs). In addition, the anti-apoptotic insulin-like growth factor (IGF)-1 and Akt-1 were also highly up-regulated in the hASCs/GCP-2 cells. In vitro cell migration and proliferation assays showed that hASCs/GCP-2-derived conditioned media (CM) significantly accelerated the migration and proliferation of fibroblast cells. Examination of in vitro endothelial differentiation showed that hASCs/GCP-2 cells spontaneously formed vascular-like structures and highly expressed endothelial-specific genes and proteins. In vivo study results of our mouse myocardial infarction (MI) model revealed that hASCs/GCP-2 implantation improved the cardiac function and reduced the infarct size. Finally, transplanted hASCs/GCP-2 cells unexpectedly differentiated into endothelial cells and the engraftment rate was significantly higher than control groups.
  
  
  CONCLUSIONS
  We suggest that overexpression of GCP-2 in stem cells has the potential to enhance their angiogenic and survival properties.
authors.affiliation: Department of Cardiology, College of Medicine, Dong-A University, 3-1, Dongdaesin-dong, Seo-Gu, Busan 602-103, South Korea. sungwhk@yahoo.co.kr
authors.forename: Sung-Whan
authors.initials: SW
authors.lastname: Kim
authors.forename: Dong-Won
authors.initials: DW
authors.lastname: Lee
authors.forename: Long-Hao
authors.initials: LH
authors.lastname: Yu
authors.forename: Hong-Zhe
authors.initials: HZ
authors.lastname: Zhang
authors.forename: Chae Eun
authors.initials: CE
authors.lastname: Kim
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Park
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Cha
authors.forename: Su-Yeong
authors.initials: SY
authors.lastname: Seo
authors.forename: Mee-Sook
authors.initials: MS
authors.lastname: Roh
authors.forename: Keun-Cheol
authors.initials: KC
authors.lastname: Lee
authors.forename: Jin-Sup
authors.initials: JS
authors.lastname: Jung
authors.forename: Moo Hyun
authors.initials: MH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D054427:Chemokine CXCL6 / Q000235:genetics / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C515503:CXCL6 protein, human; C508606:CXCL8 protein, human; D054427:Chemokine CXCL6; D017077:Culture Media, Conditioned; C066855:HGF protein, human; D016209:Interleukin-8; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt