title: Application of human mesenchymal stem cells cultured in different oxygen concentrations for treatment of graft-versus-host disease in mice.
abstract: Human mesenchymal stem cell (MSC) heterogeneity and problems associated with the ex vivo expansion of MSC are linked with the failure of MSC clinical trials. In this study, we compared the effect of MSCs cultured in different oxygen concentrations on GVHD in mice to elucidate whether hypoxia improves the immunosuppressive capacity of MSCs. Hypoxia increased the proliferative activity and the expression of several stemness and chemokine genes, such as KLF4, OCT4, C-MYC, CCL2, and CXCL10. Mice that received MSCs cultured in normoxia or hypoxia showed alleviated symptoms of GVHD and increased survival times. However, there was no significant difference in survival rates between mice that received MSCs cultured in normoxia and hypoxia. These data suggest that hypoxic culture is a useful method for maintaining and obtaining MSCs used for cell therapy and that the therapeutic potential of MSCs cultured in hypoxia warrants further investigation.
authors: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine.
authors: Dae Seong
authors: DS
authors: Kim
authors: Myoung Woo
authors: MW
authors: Lee
authors: Young Jong
authors: YJ
authors: Ko
authors: Hyun Jin
authors: HJ
authors: Park
authors: Yoo Jin
authors: YJ
authors: Park
authors: Dong-Ik
authors: DI
authors: Kim
authors: Hye Lim
authors: HL
authors: Jung
authors: Ki Woong
authors: KW
authors: Sung
authors: Hong Hoe
authors: HH
authors: Koo
authors: Keon Hee
authors: KH
authors: Yoo
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006086:Graft vs Host Disease / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D006801:Humans; D016130:Immunophenotyping; D000090062:Kruppel-Like Factor 4; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D010101:Oxygen Consumption; D010641:Phenotype
chemical_list: D015703:Antigens, CD; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4