Division of Animal Sciences, Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, USA.
Stem Cell Rev Rep. 2010 Mar;6(1):31-41. doi: 10.1007/s12015-009-9101-1.
Despite two decades of effort, establishment of pluripotent embryonic stem cells (ESC) from ungulates such as cattle and pigs has remained an elusive goal, with true ESC only successfully isolated from rodents and primates. The many reports describing ESC-like cultures from other "difficult" species has largely depended upon adopting strategies successful for mouse and human and have not yet produced a cell type that both proliferated continuously in culture without differentiation and demonstrated full pluripotent potential. These difficulties may have been exacerbated in ungulates by the lack of specific markers exclusive to inner cell mass (ICM) and its derivative the epiblast and by unique features of their preimplantation development. Especially important may have been the choice of culture condition, including growth factors, for establishing and sustaining the ESC. Recent modifications to culture medium, notably the inclusion of particular protein kinase inhibitors, have permitted ESC derivation from rat and previously "non-permissive" mouse strains. These conditions appear to stabilize the biochemical networks that sustain pluripotency and to render the cells dependent upon LIF signaling. In addition, the recent successful generation of induced pluripotent stem cells (iPSC) from pig by procedures that should be easily adapted to other species, is also likely to advance the area quickly. The pig is a particularly desirable species to create pluripotent cell lines because of its value as a biomedical model in transplantation at a time when there is mounting pressure to rush stem cells to the clinic before their safety has been adequately tested in animals.
尽管已经努力了二十年，但从牛和猪等有蹄类动物中建立多能胚胎干细胞（ESC）仍然是一个难以实现的目标，真正的 ESC 仅成功地从啮齿动物和灵长类动物中分离出来。许多描述来自其他“困难”物种的 ESC 样培养物的报告主要依赖于为小鼠和人类成功采用的策略，并且尚未产生一种既能在培养中连续增殖而不分化又能表现出完全多能潜能的细胞类型。这些困难在有蹄类动物中可能因缺乏内细胞团（ICM）及其衍生物上胚层特有的特异性标记物而加剧，并且它们的胚胎前发育具有独特的特征。选择培养条件可能尤其重要，包括建立和维持 ESC 的生长因子。最近对培养基的修改，特别是包括特定蛋白激酶抑制剂，已经允许从大鼠和以前的“非许可”小鼠品系中衍生 ESC。这些条件似乎稳定了维持多能性的生化网络，并使细胞依赖于 LIF 信号。此外，最近通过应该很容易适用于其他物种的程序从猪中成功产生诱导多能干细胞（iPSC），也可能会迅速推进该领域。猪是创建多能细胞系的特别理想的物种，因为它作为移植的生物医学模型具有价值，而此时在动物中充分测试安全性之前，将干细胞推向临床的压力越来越大。
