Extensive tissue-regenerative capacity of neonatal human keratinocyte stem cells and their progeny
Amy Li, … , Richard Redvers, Pritinder Kaur
Amy Li, … , Richard Redvers, Pritinder Kaur
Published February 1, 2004
Citation Information: J Clin Invest. 2004;113(3):390-400. https://doi.org/10.1172/JCI19140.
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Article

Extensive tissue-regenerative capacity of neonatal human keratinocyte stem cells and their progeny

Abstract

Given our recent discovery that it is possible to separate human epidermal stem cells of the skin from their more committed progeny (i.e., transit-amplifying cells and early differentiating cells) using FACS techniques, we sought to determine the comparative tissue regeneration ability of these keratinocyte progenitors. We demonstrate that the ability to regenerate a fully stratified epidermis with appropriate spatial and temporal expression of differentiation markers in a short-term in vitro organotypic culture system is an intrinsic characteristic of both epidermal stem and transit-amplifying cells, although the stem cell fraction is most capable of achieving homeostasis. Early differentiating keratinocytes exhibited limited short-term tissue regeneration under specific experimental conditions in this assay, although significant improvement was obtained by manipulating microenvironmental factors, that is, coculture with minimally passaged dermal cells or exogenous supply of the ECM protein laminin-10/11. Importantly, transplantation of all classes of keratinocyte progenitors into an in vivo setting demonstrated that tissue regeneration can be elicited from stem, transit-amplifying, and early differentiating keratinocytes for up to 10 weeks. These data illustrate that significant proliferative and tissue-regenerative capacity resides not only in keratinocyte stem cells as expected, but also in their more committed progeny, including early differentiating cells.

Authors

Amy Li, Normand Pouliot, Richard Redvers, Pritinder Kaur

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Figure 6

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KSCs and their progeny exhibit equivalent long-term epidermal tissue-reg...
KSCs and their progeny exhibit equivalent long-term epidermal tissue-regenerative capability in vivo. Transverse histological sections of rat trachea lumens lined with epithelial sheets derived from 104 human foreskin KSCs (a, d, g, and j), TA cells (b, e, h, and k), and differentiating cells (c, f, i, l) harvested at 6 weeks (a–f) and 10 weeks (g–l) after transplantation. All fractions were cotransplanted with 5 × 105 cultured keratinocytes that had received 15 Gy irradiation. For negative control transplants, uninoculated trachea at 6 weeks (m) and 5 × 105 irradiated keratinocytes alone at 6 weeks (n) and 10 weeks (o) after transplant did not yield epithelialization. ×10 magnification (a–c, g–i, and m–o); ×40 magnification (d–f and j–l). Scale bar: 100 μm. C, cartilage; L, rat trachea lumen, E, epithelial.