title: Basic fibroblast growth factor/vascular endothelial growth factor in the serum from severe burn patients stimulates the proliferation of cultured human umbilical cord mesenchymal stem cells via activation of Notch signaling pathways.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) are the leading cellular constituents used in regenerative medicine. MSCs repair and reconstruct wounds of acute traumata and radiation-induced burns through proliferation, differentiation, and trophic activity. However, repair effect of MSCs on severe burn wounds remain to be clarified because severe burns are much more complex traumata than radiation-induced burns. Survival and proliferation of MSCs in microenvironments affected by severe burns are very important for improving wound repair/regeneration. This study aimed to elucidate the survival and proliferation effects and the potential proliferation mechanism of serum from severe burn patients (BPS) on human umbilical cord MSCs (hUCMSCs) in vitro.
  
  
  METHODS
  The hUCMSCs were isolated, cultured, and identified. Next, we evaluated the effects of BPS on cell numbers, cell cycle progression, cyclin D expression, and key proteins and genes of the Notch signaling pathway. Putative mechanisms underlying the proliferation of hUCMSCs were investigated.
  
  
  RESULTS
  BPS markedly increased the number of hUCMSCs, and the results of the cell cycle studies indicated that BPS induced cell cycle progression into the M phase. Cyclin D expression was higher with BPS than in the control group. Moreover, Notch-1, a key determinant of hUCMSC activation and proliferation, and its target gene Hes-1 were overexpressed after BPS treatment. Proliferation numbers of hUCMSC, rate of proliferation period (G2/M+S), and the expression of cyclin D, Notch-1, and Hes-1 were markedly decreased by Notch signaling inhibitors (DAPT/GSI). In the case of BPS, basic fibroblast growth factor and vascular endothelial growth factor were the key factors that promoted hUCMSC proliferation.
  
  
  CONCLUSIONS
  This study provides novel evidence for the role of BPS in the survival and rapid proliferation of hUCMSCs and suggests that these cells could be used for cell therapy-based clinical applications for treating severe burns. Furthermore, hUCMSC proliferation was induced by basic fibroblast growth factor/vascular endothelial growth factor in BPS through activation of Notch signal.
authors.affiliation: From the Burn Institute, the First Affiliated Hospital of PLA General Hospital, Beijing, China.
authors.forename: Ling-Ying
authors.initials: LY
authors.lastname: Liu
authors.forename: Yu-Sen
authors.initials: YS
authors.lastname: Hou
authors.forename: Jia-Ke
authors.initials: JK
authors.lastname: Chai
authors.forename: Quan
authors.initials: Q
authors.lastname: Hu
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Duan
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Yu
authors.forename: Hui-Nan
authors.initials: HN
authors.lastname: Yin
authors.forename: Dai-Feng
authors.initials: DF
authors.lastname: Hao
authors.forename: Guang
authors.initials: G
authors.lastname: Feng
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Jun-Dong
authors.initials: JD
authors.lastname: Du
mesh_terms: D015153:Blotting, Western; D002056:Burns / Q000175:diagnosis / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D005434:Flow Cytometry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D015599:Trauma Severity Indices; D014470:Umbilical Cord / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2