Age-Dependent Depletion of Human Skin-Derived Progenitor Cells

Abstract

A major unanswered question in autologous cell therapy is the appropriate timing for cell isolation. Many of the putative target diseases arise with old age and previous evidence, mainly from animal models, suggests that the stem/progenitor cell pool decreases steadily with age. Studies with human cells have been generally hampered to date by poor sample availability. In recent years, several laboratories have reported on the existence, both in rodents and humans, of skin-derived precursor (SKP) cells with the capacity to generate neural and mesodermal progenies. This easily obtainable multipotent cell population has raised expectations for their potential use in cell therapy of neurodegeneration. However, we still lack a clear understanding of the spatiotemporal abundance and phenotype of human SKPs. Here we show an analysis of human SKP abundance and in vitro differentiation potential, by using SKPs isolated from four distinct anatomic sites (abdomen, breast, foreskin, and scalp) from 102 healthy subjects aged 8 months to 85 years. Human SKP abundance and differentiation potential decrease sharply with age, being extremely difficult to isolate, expand, and differentiate when obtained from the elderly. Our data suggest preserving human SKP cell banks early in life would be desirable for use in clinical protocols in the aging population.

The Lamina Propria of Adult Human Oral Mucosa Harbors a Novel Stem Cell Population

“…In contrast to reports on the negative effect of ageing on adult SC growth and functionality [18][19][20][21][22]57], the growth during the first 10 population doublings, the fraction of cells expressing Nanog and Oct4, the level of transcription of these factors, and the in vitro differentiation capacity of hOMSC were not affected by the donor age, thus, providing a biological explanation for the negligible ageing effect on wound healing in the elderly oral mucosa [25]. However, the increase in the doubling time at higher population doublings in elderly derived cultures suggests that mechanisms active in preserving telomeres length in EhOMSC is less effective than in YhOMSC.…”

“…hOMSC are endowed with a relatively high, telomeraseindependent self-renewing capacity and cloning efficiency compared with MSC derived from other tissue [19,22]. hOMSC produce and secrete FGF-2, EGF, VEGF, and NGF.…”

“…However, these populations do not develop to sizable proportions under normal culture conditions and their isolation and expansion require enriched substrates and culture media. In spite of their presumed existence in vivo, accumulating evidence indicates that ageing decreases the frequency, growth, and differentiation potential of adult SC [18][19][20][21][22].…”

Senescence of human skin-derived precursors regulated by Akt-FOXO3-p27KIP1/p15INK4b signaling

“…Rodent SKPs are capable of repairing damaged muscles, bones, as well as the nervous system [3][4][5]. Although human SKPs (hSKPs) can be isolated with similar protocols, their longterm expansion in vitro is defective [6,7]. We previously demonstrated that foreskin-derived adult hSKPs senesced quickly in vitro, which could be partially alleviated by enhancing PI3K-Akt pathway activity or culturing hSKPs with micro-environment-mimicking three-dimensional hydrogel scaffolds [8,9].…”

Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity screening of pharmaceuticals

“…These neural crest related ASC can also be isolated from skin of the abdomen [30], breast [30], arm [31], face [32], and scalp [33] mostly upon aesthetic interventions. These cells have a high self-renewal and high multipotent differentiation capacity.…”