Bone marrow-derived lineage-negative cells accelerate skin regeneration in vivo

Cell-based therapy is a promising strategy for promoting tissue regeneration when conventional treatments are not effective.The choice of the accessible source to obtain a sufficient cell amount and the use of suitable biomaterials to improve the cell delivery efficiency are the main tasks for safe, effective, and reliable application of stem cell therapy. In this study, we have compared the influence of bone marrow-derived Lin¯ cells on skin regeneration after local transplantation with or without type I collagen-based gel in a BALB/c mice full-thickness wound model. Lin¯ cells were isolated using magnetic-associated cell sorting and identified by flow cytometry. Cytokine gene expression was examined using real-time PCR. Our results show that the bone marrow-derived Lin¯ cell population demonstrates the properties to stimulate the skin tissue regeneration. Significant accelerated wound closure was revealed after cell transplantation (P < 0.05). Histological analysis indicated the earliest inhibition of inflammation, accelerated reepithelialization, and evenly distributed skin appendages in the neodermis after Lin¯ cell transplantation with type I collagen gel. The significant changes in mRNA levels of cytokines TNF-α, IL-10, TGF-s, and VEGF after Lin¯ cell transplantation were confirmed by RT-PCR (P < 0.05). The ability to positively control the reactions taking place during the wound healing process gives the advantage to the bone marrow Lin¯ cell population to be used as a cell source for therapy.