A Randomized, Controlled Clinical Trial of Autologous Adipose-derived Stem Cell Transplantation to Promote Mechanical Stretch-induced Skin Regeneration

Abstract

Background: The regeneration response of skin to mechanical stretching in vivo has been explored in reconstructive surgery for repairing large-scale deformities. The ability of skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous adipose-derived stem cells and mechanical stretching are combined to overcome this limitation and promote skin regeneration.Methods: This randomized, blinded, placebo-controlled clinical trial screened 22 participants undergoing tissue expansion with a presence of exhausted regeneration. Twenty eligible participants received intradermal injections with stromal vascular fraction (SVF) or placebo treatments. Follow-ups were conducted at 4, 8, and 12-weeks to assess efficacy and for 2-years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included the skin thickness at 4 and 8 weeks, the expansion index (EI) and the skin texture score at all visits. Results: The skin thickness of the SVF group was significantly higher than that of the control group at both 8 weeks (mean difference 0.78 [95% CI -1.43 to -0.11]; p = 0.018) and 12 weeks(0.65 [95% CI -1.30 to -0.01]; p = 0.046). In the SVF group, the increment of skin thickness was significant at 4 weeks (0.49 [95% CI -0.80 to -0.06]; p = 0.010) to 8 weeks (0.45 [95% CI -0.92 to 0.02]; p = 0.026) and maintained after 12 weeks, whereas that in the control group was reduced after 8 weeks (0.42 [95% CI -0.07 to 0.91]; p = 0.037). The SVF group showed higher EI increments than the control group (0.50 [95% CI -0.00 to 0.99]; p = 0.047). The skin texture scores in the SVF group were higher than those in the control group at 12 weeks. Histologically, the SVF-treated expanded skin showed more proliferating cells and blood vessels, and the volume of extracellular matrix increased. No severe adverse events occurred.Conclusions: Transplantation of autologous adipose-derived stem cells can expedite the potency of mechanical stretch-induced skin regeneration and provide clinical reconstruction with plentiful tissue. Trial registration: This trial was registered with Chinese Clinical Trial, ChiCTR2000039317 (registered 23 Oct 2020 - retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=62738).