Shi Xudong, Gipp Jerry, Bushman Wade
Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, 600 Highland Avenue, Madison, Wisconsin 53792, USA.
Dev Biol. 2007 Dec 1;312(1):396-406. doi: 10.1016/j.ydbio.2007.09.042. Epub 2007 Sep 29.
Freshly isolated mouse prostate epithelial cells regenerate fully differentiated prostate tissue when combined with embryonic urogenital sinus mesenchyme and grafted in vivo. We show here that this regenerative capacity, which has been attributed to a small population of pleuripotential progenitor epithelial cells, is rapidly lost when the cells are placed in monolayer culture but can be maintained by culture in anchorage-independent conditions. Epithelial cells placed in anchorage-independent culture formed proliferating spheres that could be serially passaged and exhibited increased expression of putative stem cell markers as compared to cells grown in monolayer culture. Epithelial cells isolated from the fetal urogenital sinus, the newborn, and adult prostate formed spheres with similar efficiency, while cells isolated from the post-castration prostate exhibited significantly higher sphere-forming abilities. When passaged spheres were recombined with E17 rat urogenital sinus mesenchyme and grafted in vivo, they generated fully differentiated mouse prostate glandular epithelium containing both p63+ basal cells and p63- luminal cells and expressing a variety of prostate-specific and terminal differentiation markers.
新鲜分离的小鼠前列腺上皮细胞与胚胎泌尿生殖窦间充质结合并移植到体内时,能再生出完全分化的前列腺组织。我们在此表明,这种再生能力一直被归因于一小群多能祖上皮细胞,当细胞置于单层培养时,这种能力会迅速丧失,但可通过在非贴壁条件下培养来维持。置于非贴壁培养的上皮细胞形成了可连续传代的增殖球,与单层培养的细胞相比,其假定干细胞标志物的表达增加。从胎儿泌尿生殖窦、新生和成年前列腺分离的上皮细胞形成球的效率相似,而从去势后前列腺分离的细胞表现出显著更高的成球能力。当传代的球与E17大鼠泌尿生殖窦间充质重新组合并移植到体内时,它们产生了完全分化的小鼠前列腺腺上皮,其中既含有p63 + 基底细胞又含有p63 - 腔面细胞,并表达多种前列腺特异性和终末分化标志物。