Extensive tissue-regenerative capacity of neonatal human keratinocyte stem cells and their progeny
Extensive tissue-regenerative capacity of neonatal human keratinocyte stem cells and their progeny
复制标题
DOI：
10.1172/jci.200419140
复制
发表时间：
2004-02-01
影响因子：
15.9
通讯作者：
Kaur, P
中科院分区：
文献类型：
--
作者：
Li, A;Pouliot, N;Kaur, P
考虑到我们最近的发现，使用FACS技术可以将皮肤的人类表皮干细胞与其更稳定的后代细胞（即转运扩增细胞和早期分化细胞）分离，我们试图确定这些角质细胞祖细胞的组织再生能力。我们证明，在短期体外器官型培养系统中，表皮干细胞和转运扩增细胞都具有再生完全分层表皮的能力，并具有适当的空间和时间表达分化标记，尽管干细胞部分最有能力实现内稳态。在本实验中，早期分化的角质形成细胞在特定的实验条件下表现出有限的短期组织再生，尽管通过操纵微环境因素（即与最小传代真皮细胞共培养或外源供应ECM蛋白层粘胶蛋白10/11）获得了显著的改善。重要的是，将所有类型的角质形成细胞祖细胞移植到体内环境中表明，可以从干细胞、转运扩增和早期分化的角质形成细胞中诱导组织再生长达10周。这些数据表明，显著的增殖和组织再生能力不仅存在于预期的角质细胞干细胞中，而且存在于它们更可靠的后代中，包括早期分化细胞。
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.