Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast by secretory factors.
BACKGROUND
Adipose-derived stem cells (ADSC) have wound-healing and antioxidant effects on human skin via secretion of growth factors and activation of dermal fibroblasts.


OBJECTIVE
Paracrine mechanism reducing ultraviolet-B (UVB)-induced wrinkles by ADSC is investigated in this study.


RESULTS
Wrinkles were induced by an eight-week UVB irradiation, and were significantly improved by the subcutaneous injection of ADSC in hairless mice. In a replica analysis, parameters involving wrinkles were improved with mid-level and high doses of ADSC (1x10(4) and 1x10(5) cells). Dermal thickness and collagen contents in the dermis also were increased in the ADSC-injected groups. To characterize the paracrine mechanism involving the antiwrinkle effect of ADSC, a conditioned medium of ADSC (ADSC-CM) was directly incubated in human dermal fibroblasts (HDF). UVB irradiation reduced the proliferation of HDF, but this was reversed by the pretreatment of ADSC-CM in a dose-dependent manner. In a cell cycle analysis, ADSC-CM decreased the UVB-induced apoptotic cell death, which was demonstrated by the reduced sub-G1 phase of HDF. In addition, the ADSC-CM increased the protein expression of collagen type I and decreased the protein level of matrix metalloproteinase 1 in HDF, which may account for the increased collagen contents in the dermis.


CONCLUSIONS
Collectively, these results indicate that the ADSC and its secretory factors are effective for UVB-induced wrinkles, and the antiwrinkle effect is mainly mediated by reducing UVB-induced apoptosis and stimulating collagen synthesis of HDF.
Kim
Won-Serk
WS
Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. prostem@empal.com
Park
Byung-Soon
BS
Park
So-Hyun
SH
Kim
Hyung-Ki
HK
Sung
Jong-Hyuk
JH
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D020405:Dermis / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects / Q000601:surgery*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D023421:Models, Animal; D019899:Paracrine Communication; D015595:Skin Aging / Q000473:pathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism*; D014466:Ultraviolet Rays
D024042:Collagen Type I; D017077:Culture Media, Conditioned; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1