A dermal niche for multipotent adult skin-derived precursor cells

Abstract

A fundamental question in stem cell research is whether cultured multipotent adult stem cells represent endogenous multipotent precursor cells. Here we address this question, focusing on SKPs, a cultured adult stem cell from the dermis that generates both neural and mesodermal progeny. We show that SKPs derive from endogenous adult dermal precursors that exhibit properties similar to embryonic neural-crest stem cells. We demonstrate that these endogenous SKPs can first be isolated from skin during embryogenesis and that they persist into adulthood, with a niche in the papillae of hair and whisker follicles. Furthermore, lineage analysis indicates that both hair and whisker follicle dermal papillae contain neural-crest-derived cells, and that SKPs from the whisker pad are of neural-crest origin. We propose that SKPs represent an endogenous embryonic precursor cell that arises in peripheral tissues such as skin during development and maintains multipotency into adulthood.

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].…”

“…The fact that different skin areas will provide progenitor cells with different specifications deserves further investigation that we are currently undertaking. Recent work has characterized a highly enriched niche of human and rodent SKPs within the DP of the hair follicle [21,22]. Although DP has the obvious advantage of being accessible in a noninvasive manner, it would also restrict donor skin areas to those rich in hair follicles.…”

“…Foreskin is a glabrous tissue with no hair follicles, a fact that led these authors to speculate about the existence of a different niche for foreskin SKPs [21,22]. To contribute on the localization pattern of SKPs in the human dermis, we analyzed consecutive sections of human foreskin, scalp, breast, and abdomen by hematoxilin-eosin staining and immunofluorescence detection of SKP markers Fibronectin, Nestin, and Vimentin, as well as p75-NTR for peripheral neurons ( other areas.…”

“…Among many others, multipotent progenitor cells (dubbed skin-derived precursors -SKPs) with potentiality to generate neural and mesodermal progeny have been described in both rodents and humans (reviewed by Fernandes et al [20]). These progenitor cells have been reported to reside in the dermal papillae (DP) of human hair follicles [21,22], their physiological role being unclear at the moment. This easily obtainable multipotent cell population has raised expectations because of their potential use in cell therapy of neurodegeneration [23][24][25][26][27][28][29].…”

Updates on stem cells and their applications in regenerative medicine

“…Thus, SKPs might represent an embryonic neural crest-related precursor. These cells would be present in skin during embryogenesis, persisting in lower numbers into adulthood (Fernandes et al, 2004, Toma et al, 2005. SKPs can be successfully isolated from human tissue, including as little as 1-2 cm 3 of foreskin and small punch biopsies from the scalp (Toma et al, 2001(Toma et al, , 2005.…”