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

BACKGROUND: Mechanical 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. METHODS: This 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. FINDINGS: The 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 cm(2) [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. INTERPRETATION: Intradermal 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.