Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose.
BACKGROUND
Glycation products accumulate during aging of slowly renewing tissue, including skin, and are suggested as an important mechanism underlying the skin aging process. Adipose-derived cells are widely used in the clinic to treat ischemic diseases and enhance wound healing. Interestingly, adipose-derived stem cells (ASCs) are also effective in anti-aging therapy, although the mechanism underlying their effects remains unknown. The purpose of the present study was to examine the anti-aging effect of ASCs in a D-galactose-induced aging animal model and to clarify the underlying mechanism.


METHODS
Six-week-old nude mice were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, mice were randomized to receive subcutaneous injections of 106 green fluorescent protein (GFP)-expressing ASCs, aminoguanidine (AG) or phosphate-buffered saline (PBS). Control mice received no treatment. We examined tissue histology and determined the activity of senescence-associated molecular markers such as superoxide dismutase (SOD) and malondialdehyde (MDA).


RESULTS
Transplanted ASCs were detectable for 14 days and their GFP signal disappeared at day 28 after injection. ASCs inhibited advanced glycation end product (AGE) levels in our animal model as well as increased the SOD level and decreased the MDA level, all of which act to reverse the aging phenotype in a similar way to AG, an inhibitor of AGE formation. Furthermore, ASCs released angiogenic factors in vivo such as vascular endothelial growth factor, suggesting a skin trophic effect.


CONCLUSIONS
These results demonstrate that ASCs may contribute to the regeneration of skin during aging. In addition, the data shows that ASCs provide a functional benefit by glycation suppression, antioxidation, and trophic effects in a mouse model of aging.
Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guang Zhou, Guang Dong, P. R. China.
Shengchang
S
Zhang
Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guang Zhou, Guang Dong, P. R. China.
Ziqing
Z
Dong
Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guang Zhou, Guang Dong, P. R. China.
Zhangsong
Z
Peng
Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guang Zhou, Guang Dong, P. R. China.
Feng
F
Lu
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000375:Aging; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned; D005690:Galactose / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006146:Guanidines / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D015595:Skin Aging / Q000187:drug effects* / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
D017077:Culture Media, Conditioned; D006146:Guanidines; D049452:Green Fluorescent Proteins; D008315:Malondialdehyde; D003094:Collagen; D013482:Superoxide Dismutase; C004479:pimagedine; D005690:Galactose