据美国媒体报道，干细胞很快将成为人类医学治疗的一种重要工具，研究人员打赌称干细胞也将成为动物园动物的一种非常有用的工具。目前，科学家正在建立一个“干细胞动物园”，用于治疗动物糖尿病和其它疾病，有助于动物繁殖。
科学家现已建立了一个“冷冻动物园”，它包含了每一个物种的不同类型细胞组织，目前它们正在组合建立一个“干细胞动物园”。斯克利普斯研究所研究员英巴尔-弗里德里希称，当前干细胞动物园中仅有两种动物，但我们已开始建立这个新的干细胞动物园。
干细胞颇具科学研究价值，这是由于它们能转换成为身体的任何类型细胞，具有特殊的“多能性(pluripotency)”。干细胞甚至可转换成为精子或者卵子细胞，有助于繁殖产生更多的物种个体。
斯克利普斯研究所的珍妮-劳瑞(Jeanne Loring)说：“最重要的是干细胞提供了作为其它项目未来的研究资源。”
濒危灭绝的干细胞
研究人员着手两种动物：鬼狒和北部白犀，鬼狒是一种基因方面接近人类的濒危灵长目动物;北部白犀基因方面与人类相差较大，但是濒危灭绝物种。
为了建立这些动物的干细胞，研究人员使用转换人类细胞多能性的一些基因，他们主张将这些基因植入动物的皮肤细胞之中。起初，他们试着使用动物自身和相关物种的基因，但经过一年多的尝试却没有成果。研究人员称，目前这种新方法并不是非常有效，每次仅能转换少量细胞成为干细胞。
干细胞疗法：可治疗珍稀物种的特殊疾病
研究人员称，这两种动物之所以被挑选是由于目前它们受益于干细胞治疗。例如：鬼狒在人工喂养期间患有糖尿症，现已证实的人类干细胞基础疗法暗示可同样治疗于灵长目动物。
北部白犀牛之所以被挑选是由于它是地球上最濒危灭绝的物种之一，目前全球仅存7只，都处于人工喂养环境，未来几年它们将无法生育繁殖，这是因为它们的数量非常少，缺乏基因多样性，这将很大程度地影响它们的存活率。
如果研究人员在冷冻动物园死亡动物皮肤细胞中提取干细胞培育出精子和卵子细胞，他们将对动物群体引入更多的基因多样性，并显著增加物种群体数量。美国加州圣地亚哥动物园研究员奥利弗-莱德(Oliver Ryder)称，避免物种灭绝最好的措施是保护物种和它们的栖息环境，但我们却一直未实施有效措施工作。
莱德指出，北部白犀牛是一个很好的例子，它们的数量非常稀少。干细胞技术有望避免它们灭绝消失，即使它们已完全从栖息环境中被抹杀。这项研究发表在9月4日出版的《自然方法》期刊上。（生物谷 Bioon.com）
doi:10.1038/nmeth.1717
PMC:
PMID:
Gametes from stem cells
Natalie de Souza
Gametes—oocytes and sperm—are arguably one of the more interesting cell types in the body. To pass on the genome to the next generation, these very specialized cells must successfully participate in the intricate dance of fertilization and then give rise to pluripotent cells that go on to generate all body tissues, including more germ cells.
The ability to make germ cells from pluripotent stem cells would aid basic studies of germline development, provide a source of germ cells to study and could in principle also be useful for assisted reproduction. In a recently published paper, Mitinori Saitou and colleagues at Kyoto University describe methods for the directed differentiation of pluripotent stem cells to primordial germ cells (PGCs) in the mouse.
PGCs go on to give rise to both male and female gametes. In the mouse, they are derived from the embryonic epiblast early in development. In previous work, researchers in Saitou's group had derived PGCs ex vivo from the isolated embryonic epiblast 5–6 days after fertilization. They reasoned that lessons learned from these previous studies could be harnessed to define a method that let them go all the way from pluripotent stem cells to PGC-like cells in vitro.
Although the so-called epiblast stem cells are in principle good candidates for generating PGC-like cells, based on their biological origin in the embryonic epiblast, this is known to occur at a very low efficiency. Could this efficiency be increased, Saitou and colleagues asked, by starting with epiblast-like cells that have not been cultured in vitro over time? The researchers set out to generate epiblast-like cells afresh from embryonic stem cells (ESCs).
They derived ESCs from mice bearing transgenes for expression of fluorescently tagged markers of PGC fate. Then, they established culture conditions (notably, this must be done serum-free) to convert these ESCs into epiblast-like cells. Finally, the researchers applied the floating three-dimensional culture conditions they had previously developed for converting isolated epiblast into PGCs and monitored germ cell fate specification from the ESC-derived cells using the fluorescent reporter transgenes. Under the right conditions, the researchers observed rapid (a few days) and efficient (about 40%) conversion of the epiblast-like cells to PGC-like cells in vitro. As they had seen previously, BMP4 signaling is key in this process.
An analysis of whole-genome expression profiles indicated that the epiblast-like stem cells are closest to in vivo embryonic day (E)5.75 epiblast and that PGC-like cells are closest to in vivo E9.5 PGCs. From this and other analyses, Saitou and colleagues conclude that they essentially recapitulated germ-cell development in vitro. Perhaps most importantly, the PGC-like cells they generate undergo functional spermatogenesis when transferred to the gonads of germ cell–deficient mice. Sperm derived from these transplanted PGCs yield viable and grossly normal offspring when used to fertilize oocytes in vitro.
The researchers generated PGC-like cells from several ESC lines, but notably, also from mouse induced pluripotent stem cells (iPSCs). What is more, they screened their cultures for cell-surface markers that can be used to enrich the in vitro–generated PGC-like cells by FACS, without the need for genetically encoded reporters.
This work has immediate value for generating large numbers of mouse PGC-like cells for basic research (several orders of magnitude more cells can be obtained this way than from mouse embryos). But in addition, one of the exciting distant vistas opened up by robust and functional in vitro germ cell differentiation is that such methods could be used to generate gametes from stem cells of other species. Indeed, in this issue of Nature Methods, Jeanne Loring and colleagues report the derivation of iPSCs from two endangered species, the silver-maned drill and the white rhinoceros. Although translating knowledge about mouse germline specification to deriving germ cells from different, nonrodent species will be a huge challenge, it is tempting to speculate that the findings of Saitou and colleagues could eventually have some bearing on efforts in other species as well.
