Simon Liz, Ekman Gail C, Kostereva Natalia, Zhang Zhen, Hess Rex A, Hofmann Marie-Claude, Cooke Paul S
Department of Veterinary Biosciences,University of Illinois, Urbana, Illinois 61802, USA.
Stem Cells. 2009 Jul;27(7):1666-75. doi: 10.1002/stem.93.
Pluripotent stem cells have great clinical potential for tissue regeneration/repair in humans. The use of embryonic stem (ES) cells is ethically controversial, leading to searches for other sources of pluripotent stem cells. Testicular spermatogonial stem cells (SSCs) produce the spermatogenic lineage. Under in vitro conditions, SSCs have the ability to give rise to pluripotent ES-like cells. We hypothesized that stem/progenitor spermatogonia could directly transdifferentiate into different tissue types if they were recombined with inductive mesenchymes from fetal/neonatal organs using a tissue separation/recombination methodology and grown in vivo. Green fluorescent protein transgenic mice were used to track cell lineages. Our results indicate that stem/progenitor spermatogonia recombined with the appropriate mesenchyme can directly transdifferentiate in vivo into tissues of all germ layers, including prostatic, uterine, and skin epithelium. In addition, transdifferentiated tissue expressed molecular, histological, and functional markers of the appropriate epithelium. The ability of stem/progenitor spermatogonia to directly generate various epithelia emphasizes their clinical potential, and if adult human SSCs have similar properties, this may have applications in human regenerative medicine.
多能干细胞在人类组织再生/修复方面具有巨大的临床潜力。胚胎干细胞(ES细胞)的使用在伦理上存在争议,这促使人们寻找其他多能干细胞来源。睾丸精原干细胞(SSCs)产生生精谱系。在体外条件下,SSCs有能力产生多能性的类ES细胞。我们假设,如果使用组织分离/重组方法将干细胞/祖细胞精原细胞与来自胎儿/新生儿器官的诱导性间充质重组,并在体内生长,它们可以直接转分化为不同的组织类型。利用绿色荧光蛋白转基因小鼠追踪细胞谱系。我们的结果表明,与适当间充质重组的干细胞/祖细胞精原细胞在体内可以直接转分化为所有胚层的组织,包括前列腺、子宫和皮肤上皮。此外,转分化组织表达了适当上皮的分子、组织学和功能标记。干细胞/祖细胞精原细胞直接生成各种上皮的能力凸显了它们的临床潜力,如果成人SSCs具有类似特性,这可能在人类再生医学中有应用价值。