Clonal analysis of nestin– vimentin+ multipotent fibroblasts isolated from human dermis

Abstract

Although several studies have shown that dermal fibroblasts possess adipogenic, osteogenic or chondrogenic differentiation potential, no study has characterized this cell population in detail, and there is as yet no evidence that a single dermal fibroblast can differentiate into all these types of cells. In this study, dermal fibroblasts were isolated from human foreskin using a regular dermal fibroblast culture system. These cells could be expended in adherent culture for over 40 cell doublings. In addition, dermal fibroblasts exhibited adipogenic, osteogenic and chondrogenic phenotypes when they were cultured in the presence of certain inducers. Importantly, clonal analysis showed that 6.4% (3/47) of the single-cell-derived clones were tripotent, 19.1% (9/47) of the clones were bipotent, and 10.6% (5/47) of the clones were unipotent. Furthermore, one of the three tested tripotent clones exhibited neurogenic and hepatogenic differentiation potential. Phenotypic analyses showed that the tripotent fibroblasts were nestin– vimentin+, which is different from the dermis-derived stem cells reported by others. These results indicate that dermal fibroblasts are a heterogeneous population containing progenitors with various levels of differentiation potential, and the nestin– vimentin+ fibroblasts may represent a novel type of multipotent adult stem cells in human dermis.

Age-Dependent Depletion of Human Skin-Derived Progenitor Cells

“…4). Taken together, our data suggest that adult human SKPs, in contrast to those obtained from the newborn and children up to 12 years of age [30,36], can be easily isolated but are not expandable under previously published culture conditions. Expansion of adult human SKPs in semisolid but not in liquid media might be a reflection of aggregate formation in the liquid dermosphere cultures.…”

“…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].…”

“…Human SKPs have been previously derived from scalp [22,34,37,38], foreskin [30,36], arm [39], and the facial area [22]. However, there has been little or no phenotypic characterization of the SKPs isolated from these areas.…”

CpG methylation of half-CRE sequences creates C/EBPα binding sites that activate some tissue-specific genes

“…S8C-S10). Dermal fibroblasts from newborn mice were differentiated into adipocytes and mRNA expression of ∼200 genes with methylated promoters increased by more than 2-fold (30). Global mRNA expression from dermal fibroblasts was similar to expression in adipocyte cultures differentiated from primary preadipocytes isolated from adult mice inguinal adipose tissue confirming that this unique differentiation system recapitulates adipocyte differentiation (SI Appendix, Fig.…”

Stem cells: novel players in the treatment of erectile dysfunction

“…73 These cells could differentiate into mesodermal lineages, including adipocytes, osteocytes and myocytes. 74 MSCs were antigenically distinct from SKPs, and when grown under the same conditions, the MSCs grew adherently (plastic adherence is one of the three hallmarks of MSCs), while SKPs grew as floating spheres.…”