A randomized, controlled clinical trial of autologous stromal vascular fraction cells transplantation to promote mechanical stretch-induced skin regeneration

Abstract

Background The regeneration response of the skin to mechanical stretching in vivo has been explored in reconstructive surgery to repair large-scale deformities. The ability of the skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous stromal vascular fraction (SVF) 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 exhausted regeneration. Twenty eligible participants received intradermal injections of the SVF or placebo treatments. Follow-ups were conducted at 4, 8, and 12 weeks to assess efficacy and at 2 years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included skin thickness at 4 and 8 weeks, the expansion index (EI), and the skin texture score at 12 weeks. 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 increase in 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 greater EI increases 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 greater than those in the control group at 12 weeks. Histologically, SVF-treated expanded skin showed more proliferating cells and blood vessels, and the extracellular matrix volume increased. No severe adverse events occurred. Conclusions Transplantation of SVF 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 the Chinese Clinical Trial Registry, ChiCTR2000039317 (registered 23 October 2020—retrospectively registered).

Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells

“…Soft-tissue expansion by mechanical stretching represents an efficient surgical procedure for skin-defect repair and organ reconstruction; however, the skin-regenerative capacity is limited ( 2 ). Stem cell therapy represents an alternative method for enhancing the regeneration of mechanically stretched skin ( 2 – 5 ). In particular, ESCs and HFBSCs located in situ play a vital role in skin regeneration and repair.…”

“…Multiple biological behaviors, including cell proliferation, dermal collagen synthesis, and angiogenesis, influence skin regeneration during the mechanical stretching process. Previous studies show that stem cell therapy using bone marrow-derived stem cells and/or adipose-derived stem cells promotes mechanically stretched skin regeneration ( 2 – 5 ). However, skin-derived stem cells, especially epidermal stem cells (ESCs) and hair follicle bulge stem cells (HFBSCs) ( 6 ), might also perform critical regenerative functions during skin expansion.…”

Mechanical Stretch Induced Skin Regeneration: Molecular and Cellular Mechanism in Skin Soft Tissue Expansion

“…Li et al transplanted SVF into the expanded skin of Wistar rats and found that SVF significantly improved the expansion efficiency and up-regulated the expressions of EGF, VEGF, and bFGF [ 134 ]. Recently, a randomized, controlled clinical trial of autologous stromal vascular fraction cells transplantation was conducted [ 135 ]. In this study, twenty patients participated in the trial and the results showed that the expanded skin receiving SVF grafts was thicker and more proliferating cells, more blood vessels, and more extracellular matrix were observed.…”

“…Both BMSC- and ADSC-induced skin growth and regeneration have been clinically tested and shown satisfactory results in skin expansion [ 135 , 156 ]. After BMSC and ADSC transplantation in patients, the expanded skin showed larger area, thicker epidermis and dermis, more blood vessels, and higher expansion index (EI).…”

Co-administration of autologous concentrated growth factor (CGF) increases skin thickness and area during tissue expansion: a randomized clinical trial

“…4 Although drugs, such as anticontractile agents, papaverine, and dimethyl sulfoxide, have been studied for promoting the expansion course, these have caused additional complications. [5][6][7] We previously reported that stem cell therapies could effectively promote stretching-induced skin regeneration 8,9 ; however, harvesting stem cells caused additional damage to the body.…”