Epithelization of skin lesions in animal model treated with mesenchymal stem cells and derivatives

摘要

Human mesenchymal stem cells (hMSCs) are used in regenerative therapies for various conditions, involving defects of one of the mesodermal lineages. We attempted to investigate the differentiation of human MSCs towards epithelial lineage and assayed the involvement of these cells in epithelization of epidermal lesions in mouse animal model. Bone marrow-derived hMSCs were grown in specific medium supplemented with EGF, KGF, FGF and IGF-2 in different concentrations for 3 weeks, expressing positive staining of early and late differentiation markers of epithelial-like cells. We used 20 B6D2F1 male mice as animal model, supplementary immunosuppressed with i.p. Dexamethasone for 3 weeks, when the skin lesion was induced. Human MSCs and epithelial-like derived cells were superficially injected at the site of the lesion in mouse model, and we followed the repair process. After 10 and 14 days, according to the cell type, animals were sacrificed and the presence of human cells (MSCs and epithelial-like cells) at the site of the injury was assessed. In mice not treated with cells the healing occurred in 15 days. Lesions treated with hMSCs stained positive for Vimentin and betal-Integrin, while treated with epithelial-like cells stained positive for E- cadherin. We may conclude that epithelial-like differentiated cells induced a faster healing of skin lesions, while undifferentiated MSCs had a minor immediate contribution to epithelization process, when injected at the site of the injury. On the long term, MSCs could have an important contribution to renewal of stem cell population within the epidermis.