Human skin‐derived stem cells migrate throughout forebrain and differentiate into astrocytes after injection into adult mouse brain

Abstract

Recent evidence indicates that neural stem cell properties can be found among a mammalian skin-derived multipotent population. A major barrier in the further characterization of the human skin-derived neural progenitors is the inability to isolate this population based on expression of cell surface markers. Our work has been devoted to purified human skin-derived stem cells that are capable of neural differentiation, based on the presence or absence of the AC133 cell surface marker. The enriched skin-derived AC133 ϩ cells express the CD34 and Thy-1 antigens. These cells cultured in a growth medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) proliferate, forming spheres, and differentiate in vitro into neurons, astrocytes, and rarely into oligodendrocytes. Single cells from sphere cultures initiated from human purified AC133 ϩ cells were replated as single cells and were able to generate new spheres, demonstrating the self-renewing ability of these stem cell populations. Brain engraftment of cells obtained from human purified AC133 ϩ -derived spheres generated different neural phenotypes: immature neurons and a most abundant population of well differentiated astrocytes. The AC133-derived astrocytes assumed perivascular locations in the frontal cortex. No donorderived oligodendrocytes were found in the transplanted mouse brains. Several donor small, rounded cells that expressed endothelial markers were found close to the host vessel and near the subventricular zone. Thus, mammalian skin AC133-derived cells behave as a multipotent population with the capacity to differentiate into neural lineages in vitro and, prevalently, endothelium and astrocytes in vivo, demonstrating the great plasticity of these cells and suggesting potential clinical application.

Isolation of a Novel Population of Multipotent Adult Stem Cells from Human Hair Follicles

“…Shih et al 43 isolated dermal stem cells from human adult scalp, Toma et al 44 isolated dermal stem cells from foreskin, and Belicchi et al 45 isolated dermal stem cells from fetal skin. 45 Neural-crest-like stem cells have been isolated from mouse whisker hair using a medium containing chick embryo extract and fetal calf serum 17,18 ; these mouse hair stem cells grew as adherent monolayer cells. However, human hair follicle-derived stem cells were not able to proliferate using their medium condition (data not shown), suggesting different biological behavior of mouse and human stem cells.…”

Age-Dependent Depletion of Human Skin-Derived Progenitor Cells

“…Several laboratories have now reported the existence of a multipotent dermal precursor cell population, the skin-derived precursor (SKP) cells (reviewed by Miller and coworkers [20,41]). Initially derived from rodents, now several groups reported isolation of SKPs from human scalp, foreskin, arm, beard and chin, in subjects ranging from fetal to old age [22,23,30,31,34,[36][37][38][39]. Transplantation of SKPs to animal models of disease has raised expectations for their potential use in human cell therapy [23][24][25][26][27][28][29].…”

“…The results showed a negative correlation (r ¼ À0.610) between Nestin-positive cells and age, which was not deemed significant (p ¼ .1081). To strengthen the argument we compared the number and/or differentiation potential of SKPs present in the foreskins of nine subjects of young (3, 9, and 10 years), middle (23,24, and 36 years), and old age (61, 84, and 85 years), respectively. Primary dermospheres obtained from these biopsies (n ¼ 9) were put into three differentiation media as described in Materials and Methods section, and comparative differentiation potentials after 14-day culture were analyzed by immunofluorescence and confocal microscopy with anti-bIII-tubulin and anti-SMA antibodies ( Fig.…”

“…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]. However, we still lack a clear understanding of the spatiotemporal abundance and phenotype of human SKPs.…”

Co-Expression of Putative Cancer Stem Cell Markers, CD133 and Nestin, in Skin Tumors

“…Among these markers, CD133 and Nestin have been described as markers of melanocytic stem cells and two of the most important surface markers with increased expression in the cancer stem cell fraction in different human malignancies, including melanoma (Klein et al, 2006;Monzani et al, 2007;Rappa et al, 2008;Al Dhaybi et al, 2010;Shakhova and Sommer, 2013). CD133 or human prominin-1/AC133 is a transmembrane glycoprotein with a molecular weight of 120 kDa that is expressed on the hematopoietic stem cells, endothelial progenitor cells and dermal-derived stem cells (Belicchi et al, 2004;Shmelkov et al, 2005).…”