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.
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.
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.
This study shows that intradermally transplanted MNCs in mechanical stretched skin is a safe and feasible clinical application.
Intradermally transplantation of MNCs can overcome the regenerative limitations of skin.
The strategy of combining stem cell and microenvironment can provide significant amounts tissue for surgical reconstruction.
Though stem cells are proved to participate in tissue regeneration, there is seldom clinical research combining stem cell and in vivo mechanotransduction to provoke skin regeneration. In this study, we introduce autologous bone marrow stem cells to mechanical stretch induced skin regeneration. The results showed that the potential of autologous stem cells in promoting skin regeneration. The application of stem cell assisted skin expansion can overcome the regenerative limitations of skin to provide significant amounts tissue for surgical reconstruction. The integration of stem cells and mechanical stretch stimuli will engender further advances in in vivo tissue regeneration.