Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages

Abstract

The adult hair follicle dermal papilla (DP) and dermal sheath (DS) cells are developmentally active cell populations with a proven role in adult hair follicle-cycling activity and unique inductive powers. In stem cell biology, the hair follicle epithelium has recently been the subject of a great deal of investigation, but up to now, the follicle dermis has been largely overlooked as a source of stem cells. Following the sporadic appearance of muscle, lipid and bone-type cells in discretely isolated follicle DP and DS cell primary cultures, we demonstrated that cultured papilla and sheath cell lines were capable of being directed to lipid and bone differentiation. Subsequently, for the first time, we produced clonal DP and DS lines that had extended proliferative capabilities. Dye exclusion has been reported to be an identifying feature of stem cells; therefore, clonal papilla and sheath lines with differing capacity to exclude rhodamine 123 were cultured in medium known to induce adipocyte and osteocyte differentiation. Both DS- and DP-derived clones showed the capacity to make lipid and to produce calcified material; however, different clones had varied behaviour and there was no obvious correlation between their stem cell capabilities and dye exclusion or selected gene expression markers. As a highly accessible source, capable of being discretely isolated, the follicle has important potentially as a stem cell source for tissue engineering and cell therapy purposes. It will also be interesting to compare follicle dermal stem cell properties with the broader stem cell capabilities discovered in skin dermis and investigate whether, as we believe, the follicle is a key dermal stem cell niche. Finally, the discovery of stem cells in the dermis may have implications for certain pathologies in which abnormal differentiation occurs in the skin.

Derivation of Functional Smooth Muscle Cells from Multipotent Human Hair Follicle Mesenchymal Stem Cells

“…Even more important, HFCs displayed multipotency as they differentiated toward fat, bone, cartilage, and SMCs, suggesting that these cells may be very similar to MSCs derived from the BM, adipose, or other tissues. Two previous studies showed that rat hair follicle cells exhibited tri-lineage differentiation potential, 7,8 but this is the first report to show that human HFCs exhibit similar properties. Although we recently showed that ovine hair follicle cells contained functional and contractile SMCs, 9 they failed to differentiate toward osteogenic, adipogenic, or chondrogenic lineages (our data not shown), suggesting that interspecies differences may be significant.…”

“…[21][22][23][24][25] Comparison between fibroblasts from interfollicular skin and hair follicles prompted some investigators to suggest that the niche of skin multipotent stem cells resides in the hair follicle. 7,26,27 Indeed, two recent studies confirmed the multipotent nature of rat hair follicle cells and showed similar differentiation potential to BM-MSCs. 7,8 Our results extent these findings to the human system and confirm that our isolation protocol renders cells from human hair follicles with the potential to differentiate toward osteogenic, adipogenic, chondrogenic, and myogenic lineage.…”

“…7,26,27 Indeed, two recent studies confirmed the multipotent nature of rat hair follicle cells and showed similar differentiation potential to BM-MSCs. 7,8 Our results extent these findings to the human system and confirm that our isolation protocol renders cells from human hair follicles with the potential to differentiate toward osteogenic, adipogenic, chondrogenic, and myogenic lineage. Therefore, the hair follicle may be a readily accessible source of autologous human MSCs (hMSCs) that can be used for tissue engineering and regenerative medicine.…”

“…6 Others showed that dermal papilla or dermal sheath cells from the rat follicles were similar to bone marrow mesenchymal stem cells (BM-MSCs) in terms of their ability to differentiate toward the adipogenic, osteogenic, and chondrogenic lineages. 7,8 In a recent study, we employed the smooth muscle alpha-actin promoter (P-aSMA) to isolate smooth muscle progenitor cells from ovine hair follicles. 9 We showed that smooth muscle progenitor cells from ovine hair follicles were highly clonogenic and expressed smoothmuscle-specific markers at the RNA and protein level.…”

Age-Dependent Depletion of Human Skin-Derived Progenitor Cells

“…As a control, both human infant and newborn rat SKPs were maintained for several passages in liquid media dermosphere culture (Fig. 2B), as expected [21,22,24,25,27,35].…”