Ultraviolet B preconditioning enhances the hair growth-promoting effects of adipose-derived stem cells via generation of reactive oxygen species.
Hypoxia induces the survival and regenerative potential of adipose-derived stem cells (ASCs), but there are tremendous needs to find alternative methods for ASC preconditioning. Therefore, this work investigated: (1) the ability of low-dose ultraviolet B (UVB) radiation to stimulate the survival, migration, and tube-forming activity of ASCs in vitro; (2) the ability of UVB preconditioning to enhance the hair growth-promoting capacity of ASCs in vivo; and (3) the mechanism of action for ASC stimulation by UVB. Although high-dose UVB decreased the proliferation of ASCs, low-dose (10 or 20 mJ/cm(2)) treatment increased their survival, migration, and tube-forming activity. In addition, low-dose UVB upregulated the expression of ASC-derived growth factors, and a culture medium conditioned by UVB-irradiated ASCs increased the proliferation of dermal papilla and outer root sheet cells. Notably, injection of UVB-preconditioned ASCs into C(3)H/HeN mice significantly induced the telogen-to-anagen transition and increased new hair weight in vivo. UVB treatment significantly increased the generation of reactive oxygen species (ROS) in cultured ASCs, and inhibition of ROS generation by diphenyleneiodonium chloride (DPI) significantly attenuated UVB-induced ASC stimulation. Furthermore, NADPH oxidase 4 (Nox4) expression was induced in ASCs by UVB irradiation, and Nox4 silencing by small interfering RNA, like DPI, significantly reduced UVB-induced ROS generation. These results suggest that the primary involvement of ROS generation in UVB-mediated ASC stimulation occurs via the Nox4 enzyme. This is the first indication that a low dose of UVB radiation and/or the control of ROS generation could potentially be incorporated into a novel ASC preconditioning method for hair regeneration.
Department of Applied Bioscience, CHA University, Seoul, Korea.
Yun-Mi
YM
Jeong
Young Kwan
YK
Sung
Wang-Kyun
WK
Kim
Ji Hye
JH
Kim
Mi Hee
MH
Kwack
Insoo
I
Yoon
Dae-Duk
DD
Kim
Jong-Hyuk
JH
Sung
D053687:Adult Stem Cells / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects*; D000818:Animals; D002465:Cell Movement / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004790:Enzyme Induction / Q000528:radiation effects; D005260:Female; D006197:Hair / Q000254:growth & development / Q000502:physiology; D018859:Hair Follicle / Q000166:cytology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D019899:Paracrine Communication / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012038:Regeneration; D033581:Stem Cell Transplantation; D050151:Subcutaneous Fat / Q000166:cytology*; D014466:Ultraviolet Rays
D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human