Plastic Surgery Research Council
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PSRC 60th Annual Meeting

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Expression of SDF-1alpha in Skin Can be Upregulated by Mechanical Stretch and Induce Migration of Bone Marrow-Derived Stem Cells into Expanded Skin
Shuangbai Zhou, M.D., Jing Wang, M.D., Chengan Chiang, M.D., Qingfeng Li, M.D., Ph.D..
Shanghai Jiao Tong University, Shanghai Ninth People's Hospital, Shanghai, China.

PURPOSE: Skin and soft tissue expansion is a procedure that stimulates skin regeneration by applying continuous mechanical stretching of normal donor skin for reconstruction purposes. We have reported that topical transplantation of bone marrow-derived mesenchymal stem cells (MSCs) can accelerate mechanical stretch induced
skin regeneration. However, it is unclear how circulating MSCs respond to mechanical stretch in skin tissue.
METHODS: MSCs from luciferase-Tg Lewis rats were transplanted into a rat tissue expansion model and tracked in vivo continuously by luminescence imaging to observe MSCs migration during skin expansion. Expression levels of chemokines including MIP-1α, TARC, SLC, CTACK, and SDF-1α were evaluated in mechanically stretched tissues, as were their related chemokine receptors in MSCs. Chemotactic assays were conducted in vitro and in vivo to assess the impact of chemokine expression on MSC migration. Expanded skin sections were stained with anti-luciferase antibody, to mark migrated MSCs, and anti-K19, CD31 antibodies, to analyze differentiation of migrated MSCs.
RESULTS: MSC migration was observed in mechanically stretched skin during in vivo cell tracking. Mechanical stretching induced temporal upregulation of chemokine expression. Among all the tested chemokines, SDF-1α showed the most significant increase in stretched skin, suggesting a strong connection to migration of MSCs. The in vitro chemotactic assay showed that conditioned medium from mechanically stretched cells induced MSC migration, that could be blocked with the CXCR4 antagonist AMD3100, as effectively as medium containing 50 ng/ml rat recombinant SDF-1α. Results from in vivo study also showed that MSC migration to mechanically stretched skin was significantly blocked by AMD3100. Moreover, migrating MSCs expressed differentiation markers, suggesting a contribution of MSCs to skin regeneration through differentiation. Expanded skin from MSC Group had significant advantage in area and epidermal thickness than that from AMD-MSC Group. More proliferating cells were found in skin sections from MSC Group.
CONCLUSION: Mechanical stretching can upregulate SDF-1α in skin and recruit circulating MSCs through the SDF-1α/CXCR4 pathway. Migrated MSCs can promote skin regeneration by differentiating into structural cells and accelerating skin cell proliferation.


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