Autologous Stem Cell Transplantation Promotes Mechanical Stretch Induced Skin Regeneration: A Randomized Phase I/II Clinical Trial

Abstract

BackgroundMechanical stretch, in term of skin expansion, can induce effective but limited in vivo skin regeneration for complex skin defect reconstruction. We propose a strategy to obtain regenerated skin by combining autologous stem cell transplantation with mechanical stretch.MethodsThis randomized, blinded placebo-controlled trial enrolled 38 adult patients undergoing skin expansion presenting with signs of exhausted regenerative capacity. Patients randomly received autologous bone marrow mononuclear cell (MNC) or placebo injections intradermally. Follow-up examinations were at 4, 8 weeks and 2 years. The primary endpoint was the volume achieved in relation to the designed size of the expander (expansion index, EI). Secondary endpoints were surface area, thickness and texture of expanded skin. This trial is registered with ClinicalTrial.gov, NCT01209611.FindingsThe MNC group had a significantly higher EI at 4 weeks (mean difference 0.59 [95% CI, 0.03–1.16]; p = 0.039) and 8 weeks (1.05 [95% CI, 0.45–1.66]; p = 0.001) versus controls. At 8 weeks, the MNC group had significantly thicker skin (epidermis: p < 0.001, dermis: p < 0.001) and higher subjective scores for skin quality/texture (24.8 [95% CI, 17.6–32.1]; p < 0.001). The MNC group had more skin surface area (70.34 cm2 [95% CI, 39.75–100.92]; p < 0.001). Patients in the MNC group gained up to the quadrupled surface area of expanded skin compared to pre-expansion at the end of expansion. No severe adverse events occurred.InterpretationIntradermal transplantation of autologous stem cells represents a safe and effective strategy to promote in vivo mechanical stretch induced skin regeneration, which can provide complex skin defect reconstruction with plentiful of tissue.

CDH1 is Identified as A Therapeutic Target for Skin Regeneration after Mechanical Loading

“…International Publisher original area) [7]. Therefore, understanding the mechanism of mechanical stretch-induced skin regeneration and finding an effective drug target would be an effective means of resolving this bottleneck.…”

“…Increasingly, mechanical forces in the microenvironment are being recognized as playing critical roles in regulating embryo development, tissue patterning, and cell behavior [1][2][3][4][5]. Skin tissue is highly sensitive to mechanical loading [6] and can be expanded after stretching [7]. Clinically, mechanical force is utilized widely to regenerate additional skin tissue for post-burn or trauma repair [8].…”

“…While mechanical stretch increases epidermal keratinocyte proliferation 9 , 10 and promotes skin regeneration 11 , 12 , the underlying cellular and molecular mechanisms have not been studied in-depth. Nevertheless, the stretch-induced skin regenerative capacity is limited (usually less than 2-3-fold of its original area) 7 . Therefore, understanding the mechanism of mechanical stretch-induced skin regeneration and finding an effective drug target would be an effective means of resolving this bottleneck.…”

Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche

“…[ 39 ] Furthermore, a randomized phase I/II clinical trial demonstrated that intradermal transplantation of autologous stem cells was an effective and safe strategy to promote in vivo mechanical stretch induced skin regeneration, and they can provide complex skin defect reconstruction with plentiful of tissue. [ 40 ]…”

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

“…Skin thickness was measured at eight evenly spaced measurement points along the longitudinal axis using a duplex ultrasonic scanner [ 33 ]. In ultrasound images, skin appears as a well-defined, linear echogenic band between the air-epidermal band and the low echo-level hypodermal band.…”