Skin-Derived Stem Cells in Human Scar Tissues: A Novel Isolation and Proliferation Technique and Their Differentiation Potential to Neurogenic Progenitor Cells

Abstract

Adult tissues contain stem cells that can transdifferentiate into other cell lineages besides forming differentiated cells of their own tissue of origin. However, human adult skin-derived stem cells have a very low efficiency. Here we established a novel culture system involving bone morphogenetic protein-4 and a floating culture system with sphere-producing medium that can enrich adult stem-cell populations in vitro. Adult stem cells were isolated from useless human scar tissue. Like mesenchymal stem cells, cultured human scar tissue-derived stem cells (hSTSCs) altered their morphology and significantly increased the number of Nestin-positive cells in proportion to the alkaline phosphatase–positive cell ratio. Moreover, the expression of the pluripotency regulator Oct-4 and its target transcripts, Sox-2, c-kit, and Rex-1, was also stimulated by this culture system. Differentiation of neurogenic progenitor cells using basic fibroblast growth factor and Neurogen 2 was successfully performed in vitro more rapidly than previous reports. Neuronal differentiation results showed that our hSTSCs expressed marker of neurogenic genes, such as glial fibrillary acid protein, neural cell adhesion molecules, neuron filament-M, and microtubule-associated protein 2. These results suggest that bone morphogenetic protein-4 and the floating culture system with sphere-producing medium induced significant proliferation of hSTSCs and mediated reprogramming of the cells from adult somatic tissue into precursor state to some degree. It is thought that this new culture system might be a simple, effective, and easily manageable process for regenerative tissue repair and autotransplantation.