TGF-ß2 and collagen play pivotal roles in the spheroid formation and anti-aging of human dermal papilla cells.

Dermal papilla cells (DPCs) tend to aggregate both in vitro and in vivo, which increases the hair inductivity of DPCs. However, the underlying mechanism of spheroid formation is unknown. We investigated whether collagen expression in human DPCs (hDPCs) is involved in the spheroid formation and hair inductivity of hDPCs and further examined the underlying molecular mechanism of collagen upregulation. The expression of diverse collagens, such as COL13A1 and COL15A1, was upregulated in three dimensional (3D)-cultured or intact DPCs, compared to 2D-cultured hDPCs. This collagen expression was a downregulated in aged hair follicle, and aged DPCs were difficult to aggregate. Blocking of COL13A1 and COL15A1 by small interfering RNA reduced aggregation, while induced senescence of hDPCs in vitro. Further, transforming growth factor-ß2 (TGF-ß2) expression decreases with aging, and is involved in regulating the expression of COL13A1 and COL15A1. Addition of recombinant TGF-ß2 delayed cellular senescence, and recovered spheroid formation in aged hDPCs by upregulating collagen levels. On the contrary, knock-out of TGF-ß2 induced the aging of DPCs, and inhibited spheroid formation. These results suggested that COL13A1 and COL15A1 expression is downregulated with aging in DPCs, and upregulation of collagen by TGF-ß2 induces the spheroid formation of DPCs. Therefore, TGF-ß2 supplement in DPC culture medium could enhance the maintenance and hair inductivity of DPCs.

Regulatory role of microRNAs in the proliferation and differentiation of adipose-derived stem cells.

Adipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells obtained from stromal-vascular fraction of adipose tissue. ASCs are a promising resource for cell therapy due to their simple isolation, extensive expansion potential, and low immunogenicity. ASCs repair and regenerate damaged tissue by direct differentiation, whereas many other approaches rely on the secretion of paracrine factors. miRNAs target mRNAs for cleavage or translational repression, and have been shown to play critical roles in the regulation of stem cell proliferation and differentiation. The miRNA expression profile of ASCs varies according to the isolation and culturing method, and more than 40 different miRNAs have been reported to regulate ASC proliferation and differentiation. Therefore, this review summarizes the ASC-related miRNAs and their pivotal roles in regulating the proliferation and differentiation of ASCs. A comprehensive understanding of the effects of miRNAs on the proliferation and differentiation of ASCs is important and useful to enhance the regenerative potential of ASCs.