日本研究人员8月4日报告说,他们成功将实验鼠胚胎干细胞转化为健康精子,并最终培育出健康且具生殖能力的小老鼠。这项研究有望为男性不育者带来福音。
日本京都大学教授斋藤通纪等人在美国《细胞》杂志网络版上说,他们首先将实验鼠胚胎干细胞转化为原始生殖细胞,并将其植入不能正常产生精子的实验鼠体内,原始生殖细胞此后开始产生正常形态的精子,这些精子能够使卵子受精。
研究人员写道:“植入受精卵的受体实验鼠产下的后代很健康,发育正常,无论雌雄,都具有生殖能力。”
利用干细胞培养“人造精子”的研究由来已久。早在2003年,就有数个研究小组声称制造出“人造精子”,但让实验鼠怀孕的努力以失败告终。
2006年,英国纽卡斯尔大学一个研究小组利用胚胎干细胞制造出“人造精子”,并培育7只小老鼠,但7只小老鼠均出现健康问题并夭折。3年后,这个研究小组又宣布成功利用人类干细胞培育出成熟精子,不过这篇论文很快因两段内容涉嫌剽窃被撤销。
一些科学家对成功培养“人造精子”的消息感到无比激动,称之为“巨大突破”。但也有科学家说,这一技术应用于人类之前,还需要克服不少技术和伦理难题。参与研究的斋藤通纪也表示,要将这一技术应用在人类身上“仍有很长一段路要走”。(生物谷 Bioon.com)
doi:10.1016/j.cell.2011.06.052
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Reconstitution of the Mouse Germ Cell Specification Pathway in Culture by Pluripotent Stem Cells
Katsuhiko Hayashi, Hiroshi Ohta, Kazuki Kurimoto, Shinya Aramaki, Mitinori Saitou
The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development. We demonstrate here the generation of primordial germ cell-like cells (PGCLCs) in mice with robust capacity for spermatogenesis. PGCLCs were generated from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pregastrulating epiblasts but distinct from epiblast stem cells (EpiSCs). Reflecting epiblast development, EpiLC induction from ESCs/iPSCs is a progressive process, and EpiLCs highly competent for the PGC fate are a transient entity. The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs meticulously capture those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-β3 and SSEA1 as markers that allow the isolation of PGCLCs with spermatogenic capacity from tumorigenic undifferentiated cells. Our findings provide a paradigm for the first step of in vitro gametogenesis.