| Stem cells that have the self-renewal potential and multilineage differentiation capacity are the relevant cells in regenerative medicine and have attracted special attention. In recent years, multipotent stem cells from several adult tissues have been identified and have shown promising therapeutic implications. In this regard, bone marrow mesenchymal stem cells have been the model of choice for many researchers. Simultaneously, it is also very important to investigate alternative sources of adult multipotent stem cells. Skin is the biggest organ in the body. Skin stem cell biology has been a focus of increasing interest in current life science. There is increasing evidence that dermis contains multipotent stem cells. Several reports from our group and other groups have indicated that multipotent cells can be isolated from adult mammalian dermis and have been shown to have the capacity to produce neural as well as mesodermal derivatives. Given its easy accessibility, these cells may provide an accessible source of stem cells for cell transplantation gene therapy and tissue engineering. However, the biological properties and the therapeutic implications of multipotent stem cells from the dermis are not well known.Wound healing is a complex process requiring the collaborative efforts of many different cell lineages and the local environment. During the healing process, different cell types are activated by the environment and migrate and proliferate at the wound site. Present studies have indicated that it is the specific tissue environment that determines the plasticity of stem cells in vivo. Dermis mainly consists of fibroblasts and collagen-rich extracellular matrix, plays complex physical functions, provides support and nourishment for the skin. Considering that the origin of wound healing fibroblasts is still debated, we hypothesize that multipotent stem cells in dermis may represent a progenitor fibroblast population that are activated in response to wounding. Up to now, the activation of epithelial cells, fibroblasts and endothelial cells has been observed, but little is known about the roles and regulations of dermis-derived multipotent stem cells in wound healing. Also as an alternative promising source of adult multipotent stem cells, whether dermis-derived multipotent cells may sharesome similar properties with other adult multipotent stem cells is still fa interest, fa this paper, we identified clonal populations of multipotent stem cells from the dermis of rat and humans, performed a series of experiments to study their biological properties, the promoting effects on wound repair and hematopoietic recovery fa several types of animal models.The main results and conclusions are summarized as follows:1. Stem cells with multipotent differentiation capacity fa specific inducing media were identified from newborn rat dermis, human foreskin dermis and human hair pappila cells by their adherence to the culture plastic. These results indicate that multipotent stem cells exist in rat and human dermis, and widely distributed fa non-follicle dermis and follicle dermis. A clonal population of multipotent stem cells (termed as dermal multipotent cells, DMCs) was further isolated from newborn rat dermis and their biological properties fa vitro and functional activities fa vivo were studied. Phenotype analysis by specific antibodies showed that DMCs were negative for some lineage-specific surface markers including pan-cytokeratin, cytokeratin19, Factor VIII, CD31, CD45, CD34, a-smooth muscle actin (a-SMA), desmin, collagen II and nestfa, but DMCs were positive for CD59, CD90, CD44, VCAM-1 and ICAM-1. These cells were also positive for vimentin, but were negative for CD4. There was no obvious difference of the growth pattern and differentiation capacity between cells of the third and tenth passage. DMCs expressed multilineage transcripts fa culture by DNA microarray analysis and could be induced to differentiate into various cell types, including osteocytes, chondrocytes, adipocytes and neurons. Mixed colla...
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