據(jù)美國(guó)媒體報(bào)道,，干細(xì)胞很快將成為人類(lèi)醫(yī)學(xué)治療的一種重要工具,，研究人員打賭稱(chēng)干細(xì)胞也將成為動(dòng)物園動(dòng)物的一種非常有用的工具,。目前,，科學(xué)家正在建立一個(gè)“干細(xì)胞動(dòng)物園”,，用于治療動(dòng)物糖尿病和其它疾病,，有助于動(dòng)物繁殖,。
科學(xué)家現(xiàn)已建立了一個(gè)“冷凍動(dòng)物園”，它包含了每一個(gè)物種的不同類(lèi)型細(xì)胞組織,，目前它們正在組合建立一個(gè)“干細(xì)胞動(dòng)物園”,。斯克利普斯研究所研究員英巴爾-弗里德里希稱(chēng)，當(dāng)前干細(xì)胞動(dòng)物園中僅有兩種動(dòng)物,，但我們已開(kāi)始建立這個(gè)新的干細(xì)胞動(dòng)物園,。
干細(xì)胞頗具科學(xué)研究?jī)r(jià)值，這是由于它們能轉(zhuǎn)換成為身體的任何類(lèi)型細(xì)胞,，具有特殊的“多能性(pluripotency)”,。干細(xì)胞甚至可轉(zhuǎn)換成為精子或者卵子細(xì)胞，有助于繁殖產(chǎn)生更多的物種個(gè)體,。
斯克利普斯研究所的珍妮-勞瑞(Jeanne Loring)說(shuō)：“最重要的是干細(xì)胞提供了作為其它項(xiàng)目未來(lái)的研究資源,。”
瀕危滅絕的干細(xì)胞
研究人員著手兩種動(dòng)物：鬼狒和北部白犀，鬼狒是一種基因方面接近人類(lèi)的瀕危靈長(zhǎng)目動(dòng)物;北部白犀基因方面與人類(lèi)相差較大,，但是瀕危滅絕物種,。
為了建立這些動(dòng)物的干細(xì)胞，研究人員使用轉(zhuǎn)換人類(lèi)細(xì)胞多能性的一些基因,，他們主張將這些基因植入動(dòng)物的皮膚細(xì)胞之中,。起初，他們?cè)囍褂脛?dòng)物自身和相關(guān)物種的基因,，但經(jīng)過(guò)一年多的嘗試卻沒(méi)有成果,。研究人員稱(chēng)，目前這種新方法并不是非常有效,，每次僅能轉(zhuǎn)換少量細(xì)胞成為干細(xì)胞,。
干細(xì)胞療法：可治療珍稀物種的特殊疾病
研究人員稱(chēng)，這兩種動(dòng)物之所以被挑選是由于目前它們受益于干細(xì)胞治療,。例如：鬼狒在人工喂養(yǎng)期間患有糖尿癥,，現(xiàn)已證實(shí)的人類(lèi)干細(xì)胞基礎(chǔ)療法暗示可同樣治療于靈長(zhǎng)目動(dòng)物。
北部白犀牛之所以被挑選是由于它是地球上最瀕危滅絕的物種之一，目前全球僅存7只,，都處于人工喂養(yǎng)環(huán)境,，未來(lái)幾年它們將無(wú)法生育繁殖,，這是因?yàn)樗鼈兊臄?shù)量非常少,，缺乏基因多樣性，這將很大程度地影響它們的存活率,。
如果研究人員在冷凍動(dòng)物園死亡動(dòng)物皮膚細(xì)胞中提取干細(xì)胞培育出精子和卵子細(xì)胞,，他們將對(duì)動(dòng)物群體引入更多的基因多樣性，并顯著增加物種群體數(shù)量,。美國(guó)加州圣地亞哥動(dòng)物園研究員奧利弗-萊德(Oliver Ryder)稱(chēng),，避免物種滅絕最好的措施是保護(hù)物種和它們的棲息環(huán)境，但我們卻一直未實(shí)施有效措施工作,。
萊德指出,，北部白犀牛是一個(gè)很好的例子，它們的數(shù)量非常稀少,。干細(xì)胞技術(shù)有望避免它們滅絕消失,，即使它們已完全從棲息環(huán)境中被抹殺。這項(xiàng)研究發(fā)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
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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.
