Study Of Mechanism Involved In Bone Marrow Stem Cell Promoting Expanded Skin Regeneration And Related Clinical Research

Repairing skin deficiency due to trauma or diseases still remains as a clinical challenge.The search for adequate autologous donor skins for defect reconstruction has been a focus inmodern reconstructive surgery. Skin and soft tissue expansion has been a good solution to thisproblem. By implanting a tissue expander and inflating it with saline, mechanical stretch takesplace, and in vivo skin regeneration is initiated, producing additional skin with perfectlymatched color and texture for a variety of repairs and reconstructions. In spite of the advantagesof skin expansion, its clinical potential has been limited by the inherent regeneration capabilityof expanded skin. In many cases, expansion aiming for extensive skin, which is beyond the skingrowth capacity often ends up with thinning and deterioration in skin texture or even ulcer,ultimately leading to failure of the procedure. The core of inspiring this traditional method is tobreak the limitation in regenerative capacity and promote the sustainable regeneration of skin.The assist of stem cell transplantation may overcome the obstacle in this treatment and bepromote it to a novel regenerative medicinal. In this project, we explore the effect andmechanism of bone marrow stem cells promoting expanded skin regeneration in animal modelsand clinical trial.Using the skin expansion model, we studied the role of circulating MSCs in expanded skinregeneration. The results showed that intravenous transplantation of MSCs could effectivelypromote expanded skin regeneration. By marking transplanted MSCs with special antibody, wefound that intravenously transplanted MSCs could be recruited and migrate to expanded skin,and participate in skin regeneration by differentiating into structural cells. Furthermore, we found that mechanical stretching induced temporal upregulation of chemokine expression.Among all the tested chemokines, SDF-1α showed the most significant increase in stretchedskin. By interaction with CXCR4on MSCs, SDF-1α could effectively induce MSCs migrationinto expanded skin. We further verified that MSCs recruited by SDF-1α/CXCR4pathway haveimportant role in promoting expanded skin regeneration.In the clinical trial, patients who presented with deteriorated expanded skin were recruited.The patients were randomly assigned to receive intradermal autologous MNC transplantationand placebo injections. MNC transplantation intradermally to expanded skin is safe and feasiblein the clinical setting. The study also demonstrated that MNC transplantation can effectivelypromote the regeneration of skin induced by mechanical stretch.This project explored and discussed the mechanism of stem cells promoting expanded skinregeneration, providing the translation of this novel technique a solid support. The findings ofthis clinical trial suggest that the transplantation of autologous stem cells could break thelimitation of regenerative capacity in skin tissue and provoke the traditional skin expansiontreatment into a new regenerative medicine technique. This new treatment would provide agiant amount of regenerated skin with normal appearance and integral function to patients withlimited donor skin area. Moreover, this new treatment which integrates the stem cells and thein vivo microenvironment would give the inspiration to future regenerative medicine.