title: N-cadherin determines individual variations in the therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells in a rat model of myocardial infarction.
abstract: In this study, we established and characterized human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) from four different donors. However, the hUCB-MSCs showed remarkable variations in their therapeutic efficacy for repairing rat infarcted myocardium (including the process of angiogenesis) 8 weeks after transplantation. In addition, we observed that the level of vascular endothelial growth factor (VEGF) is correlated with the therapeutic efficacy of the four hUCB-MSCs. Next, to investigate the practical application of hUCB-MSCs, we searched for surface signature molecules that could serve as indicators of therapeutic efficacy. The gene for N-cadherin was the only cell surface gene that was highly expressed in the most effective hUCB-MSCs, both at the transcriptional and translational levels. We observed downregulation and upregulation of VEGF in response to N-cadherin blocking and N-cadherin overexpression, respectively. Activation of extracellular signal-regulated kinase (ERK), but not protein kinase B, was increased when N-cadherin expression was increased, whereas disruption of N-cadherin-mediated cell-cell contact induced suppression of ERK activation and led to VEGF downregulation. Moreover, by investigating hUCB-MSCs overexpressing N-cadherin or N-cadherin knockdown hUCB-MSCs, we confirmed the in vivo function of N-cadherin. In addition, we observed that DiI-labeled hUCB-MSCs express N-cadherin in the peri-infarct area and interact with cardiomyocytes.
authors: National Research Laboratory for Cardiovascular Stem Cells and IRICT, Seoul National University Hospital, Seoul, Korea.
authors: Eun Ju
authors: EJ
authors: Lee
authors: Eue-Keun
authors: EK
authors: Choi
authors: Soo Kyoung
authors: SK
authors: Kang
authors: Gi-Hwan
authors: GH
authors: Kim
authors: Ju Young
authors: JY
authors: Park
authors: Hyun-Jae
authors: HJ
authors: Kang
authors: Sae-Won
authors: SW
authors: Lee
authors: Keum-Hyun
authors: KH
authors: Kim
authors: Jin Sook
authors: JS
authors: Kwon
authors: Ki Hong
authors: KH
authors: Lee
authors: Youngkeun
authors: Y
authors: Ahn
authors: Ho-Jae
authors: HJ
authors: Lee
authors: Hyun-Jai
authors: HJ
authors: Cho
authors: Soo Jin
authors: SJ
authors: Choi
authors: Won Il
authors: WI
authors: Oh
authors: Young-Bae
authors: YB
authors: Park
authors: Hyo-Soo
authors: HS
authors: Kim
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000235:genetics; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D020869:Gene Expression Profiling; D006321:Heart / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D015398:Signal Transduction; D014019:Tissue Donors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D015820:Cadherins; D042461:Vascular Endothelial Growth Factor A; D048049:Extracellular Signal-Regulated MAP Kinases