<Original> Human Adipose-derived Stem Cells Induce Cell Senescence in a Keloid Model

[Abstract] Keloid disorder is primarily characterized by unremitting accumulation of collagen fiber. An effective treatment method and the underlying mechanism needs to be explored. In this study, human adipose-derived stem cells (ADSCs) were cultured with either keloid or normal fibroblasts in vitro. For in vivo study, keloid fibroblasts were seeded on a honeycomb collagen sponge, which was implanted for 8 weeks in severely immunodeficient (NOD/SCID) mice (KF group). ADSCs were then locally administered in this model (KF-ADSC group), and the effect on keloid fibroblasts was immunohistochemically investigated. The in vitro study demonstrated that transforming growth factor (TGF)-β and collagen production decreased during incubation and the number of SA-β-galactosidase+ cells increased in keloid fibroblasts by ADSCs. The in vivo study revealed that the numbers of α-SMA+, CD26+, PCNA+ cells, the sum intensity of TGF-β+, and collagen production were significantly reduced in KF-ADSC compared with those in KF (P<0.01). Unlike KF, positive responses to p16 INK 4a and tumor necrosis factor (TNF)-α were found in myofibroblasts/fibroblasts of the KF-ADSC groups, indicative of cell senescence in keloid fibroblasts by ADSCs (P<0.01). These results indicate that ADSCs inhibited cell proliferation and collagen production of keloid fibroblasts in vitro and in vivo, possibly through cell senescence. Key messages: The underlying mechanism and an effective treatment need to be explored in keloid. The aim of this study is to search for a potential role of adipose-derived stem cell (ADSCs) in inhibiting keloid formation in vitro and in vivo. 72 severely immunodeficient mice were used for in vivo study. Positive responses to SA-β-galactosidase and p16 INK 4a were found in the keloid fibroblasts treated with ADCSs, indicating that ADSCs inhibited cell proliferation and collagen production of keloid fibroblasts in vitro and in vivo, possibly through cell senescence.