2009年12月18日,,北京生命科學(xué)研究所高紹榮實(shí)驗(yàn)室在Stem Cells雜志在線發(fā)表題為“Generation of Histocompatible Androgenetic Embryonic Stem Cells Using Spermatogenic Cells”的研究論文,。該論文報(bào)道了采用核移植方法將不同階段的生精細(xì)胞注入去核卵細(xì)胞從而成功獲得了具有供體組織相容性的孤雄胚胎干細(xì)胞(Androgentic Enbryonic Stem Cells, aES cells)。首次證實(shí)不同階段生精細(xì)胞都能制備孤雄胚胎干細(xì)胞,,是組織細(xì)胞替代治療的潛在干細(xì)胞來源之一,。且不涉及毀壞正常受精胚胎,規(guī)避了胚胎干細(xì)胞研究應(yīng)用中這一引人關(guān)注的倫理問題,。
正常胚胎干細(xì)胞來自囊胚內(nèi)細(xì)胞團(tuán)(Inner Cell Mass,ICM), 具有無限增殖能力以及能分化產(chǎn)生各種細(xì)胞和組織的全能性,。因而胚胎干細(xì)胞具有巨大的潛能用于治療組織細(xì)胞退化性疾病和遺傳性疾病。倫理問題以及期望獲得病人自身胚胎干細(xì)胞的需求,,促使進(jìn)一步尋找其它來源的胚胎樣干細(xì)胞制備方法,。單性胚胎干細(xì)胞就是其中之一,,其中孤雄胚胎干細(xì)胞就是特定制備雄性胚胎干細(xì)胞。
以往報(bào)道的孤雄胚胎干細(xì)胞制備方法是通過去除雌原核后的兩個(gè)受精卵融合而來的,。一方面仍然存在毀壞胚胎的倫理問題,,另一方面制備的孤雄胚胎干細(xì)胞全能性不盡人意。高紹榮實(shí)驗(yàn)室采用細(xì)胞核移植的方法,,將初級(jí)精母細(xì)胞(Primary spermatocytes,PS),,圓精細(xì)胞(round spermatids,RS)和成熟精子(Mature spermatozoa,S)三種不同階段的生精細(xì)胞分別注入去核卵細(xì)胞,構(gòu)建僅含有供體雄性基因組的重組胚胎,,即孤雄胚胎,。由此分別制備了PS來源的a(PS)ES, RS來源的a(RS)ES和S來源的a(S)ES三類aES細(xì)胞。經(jīng)多能基因mRNA分析和多能因子表達(dá)分析,,以及畸胎瘤實(shí)驗(yàn)證實(shí)了這三類aES細(xì)胞具有胚胎干細(xì)胞的全能性,。而且還獲得了a(PS)ES和a(RS)ES細(xì)胞的嵌合體小鼠。研究中還發(fā)現(xiàn)隨著培養(yǎng)時(shí)間的延長(zhǎng)孤雄胚胎干細(xì)胞獲得了和正常胚胎干細(xì)胞相似的基因印跡狀態(tài)和相似的印跡基因表達(dá)水平,。體內(nèi)aES細(xì)胞移植實(shí)驗(yàn)表明獲得的胚胎干細(xì)胞具有與供體鼠MHC組織相容的能力,。該研究表明孤雄胚胎干細(xì)胞能夠來源于生精細(xì)胞的不同階段,是獲得雄性自體MHC組織相容性胚胎干細(xì)胞的有效途徑之一,。(生物谷Bioon.com)
更多干細(xì)胞研究:
Nature:E2fs可激活干細(xì)胞分化
The Lancet:利用胚胎干細(xì)胞成功誘導(dǎo)完整表皮
Nature:利用干細(xì)胞培育出人工精子卵子
Science:成功用單倍體胚胎干細(xì)胞培育出半克隆魚
Nature:iPS細(xì)胞轉(zhuǎn)化率提高約百倍
干細(xì)胞研究匯總
干細(xì)胞動(dòng)態(tài):
干細(xì)胞研究:雷聲大,,雨點(diǎn)也大
美國(guó)將開展世界首次胚胎干細(xì)胞療法臨床實(shí)驗(yàn)
美國(guó)批準(zhǔn)13個(gè)人類胚胎干細(xì)胞系用于研究
人類胚胎干細(xì)胞(hESCs)研究的喜訊 愛爾蘭宣布子宮外的人類胚胎不再受憲法保護(hù)
美國(guó)第二項(xiàng)干細(xì)胞臨床試驗(yàn)
生物谷推薦原始出處:
STEM CELLS 17 Dec 2009 DOI:10.1002/stem.283
Generation of Histocompatible Androgenetic Embryonic Stem Cells Using Spermatogenic Cells
Qingguo Zhao 1, Jianle Wang 1 2, Yu Zhang 1, Zhaohui Kou 1, Sheng Liu 1, Shaorong Gao 1 *
1National Institute of Biological Sciences, Beijing 102206, China
2State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
Androgenetic embryonic stem (aES) cells, produced by pronuclear transplantation, offer an important autologous pluripotent stem cell source. However, the isolation of aES cells, particularly individual-specific aES cells, using fertilized embryos has limited the practical applications of this technology in humans. In the present study, we applied a new approach, essentially described as somatic cell nuclear transfer (SCNT), and generated three types of aES cell lines using spermatogenic cells including primary spermatocytes (PS), round spermatids (RS) and mature spermatozoa (S) as donor cells, omitting the need to use fertilized embryos. Although abnormality of chimeras and absent germline competency indicated that all three types of aES cells exhibiting limited pluripotency, the epigenetic status of the aES cell lines tended to resemble normal ES cells during long-term culture and some parental-specific imprinted genes were expressed at levels comparable to those of normal ES cells. Furthermore, the histocompatibility of the aES cells was investigated by transplanting the differentiation progenies of the aES cells into MHC-matched and mismatched recipient mice. The results indicated that these aES cells were histocompatible with MHC-matched mice after transplantation. Our study provided evidence indicating that MHC-competent autologous aES cells could be generated from different spermatogenic cells using nuclear transfer into oocytes that could avoid using fertilized embryos.