Role of CD9 in proliferation and proangiogenic action of human adipose-derived mesenchymal stem cells.
CD9 belongs to the tetraspanin family and is involved in cell motility, osteoclastogenesis, metastasis, neurite outgrowth, myotube formation, and sperm-egg fusion. CD9 also promotes juxtacrine signaling involved in proliferation and attachment. Varying degrees of CD9 expression have been found in human mesenchymal stem cells. In this study, we determined the functional roles of CD9 in human adipose-derived mesenchymal stem cells (hASCs). The CD9 expression in hASCs was down-regulated during culture expansion. A colony-forming unit assay revealed that the clonal expandability of hASCs was directly correlated with the CD9 expression level of the colony. The CD9(high) cells exhibited an increased ability to proliferate, increased cell adhesiveness, and better in vitro tube formation than the CD9(low) cells. The cellular proliferation and attachment of the CD9(high) cells were inhibited upon treatment with a blocking antibody against CD9 and the transduction of a CD9 miRNA lentivirus. The CD9(high) cells showed higher NF-kappaB promoter activity and higher levels of intercellular adhesion molecule 1 than the CD9(low) cells. Reverse transcription-polymerase chain reaction analysis revealed higher endothelial nitric oxide synthase expression in the CD9(high) cells than in the CD9(low) cells. The engraftment and the proangiogenic action of hASCs in a murine model of hindlimb ischemia were significantly higher in the CD9(high) cells than in the CD9(low) cells. This study indicates that CD9 plays roles in cell proliferation and attachment in vitro as well as in in vivo engraftment and that it can be considered as a useful marker to predict the in vivo efficacy of hASCs.
Kim
Yeon Jeong
YJ
Department of Physiology, School of Medicine, Pusan National University, 1 Ga, Ami-Dong, Suh-Gu, Pusan 602-739, South Korea.
Yu
Ji Min
JM
Joo
Hye Joon
HJ
Kim
Hoe Kyu
HK
Cho
Hyun Hwa
HH
Bae
Yong Chan
YC
Jung
Jin Sup
JS
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D060245:Tetraspanin 29
D015703:Antigens, CD; D015415:Biomarkers; C554869:CD9 protein, human; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29