GONG Seung Pyo, LEE Jae Hee, LIM Jeong Mook
WCU Biomodulation Program, Seoul National University, Seoul, South Korea.
J Reprod Dev. 2010 Oct;56(5):481-94. doi: 10.1262/jrd.10-043e.
Somatic cell nuclear transfer, the first established technique for producing patient-specific autologous stem cells, inevitably requires the sacrifice of viable embryos. To circumvent the serious ethical issues associated with this use of embryos, researchers have developed several alternative methods for the production of histocompatible stem cells. In our research, we have used two methods to derive histocompatible stem cells from murine ovarian tissue. First, we have established autologous stem cells by culturing degeneration-fated preantral follicles to produce developmentally competent, mature oocytes and then parthenogenetically activating these mature oocytes to acquire genetic homogeneity. Second, we have used cell-to-cell interactions to derive stem cells from ovarian stromal cells without undertaking genetic modification. We have successfully derived autologous murine stem cells by manipulating primary and early secondary follicles in vitro, and this method has proved successful even for follicles retrieved from aged ovaries. Furthermore, we believe that it will be possible to isolate stem cells directly from non-germline ovarian tissue or to derive stem cells by culturing the ovarian cells with other somatic cells. If achieved, these aims will greatly advance the development of induced pluripotent stem cell technology, as well as tissue-specific stem cell research. In this review, we introduce the relevant technologies for establishing histocompatible stem cells from ovarian tissue cells without undertaking genetic manipulation and review the current limitations of, and future research directions in, stem cell biology.
体细胞核移植是首个用于产生患者特异性自体干细胞的成熟技术，但不可避免地需要牺牲活胚胎。为规避与胚胎这种用途相关的严重伦理问题，研究人员已开发出几种生产组织相容性干细胞的替代方法。在我们的研究中，我们使用了两种方法从鼠卵巢组织中获得组织相容性干细胞。首先，我们通过培养注定退化的窦前卵泡以产生具有发育能力的成熟卵母细胞，然后孤雌激活这些成熟卵母细胞以获得基因同质性，从而建立了自体干细胞。其次，我们利用细胞间相互作用从卵巢基质细胞中获得干细胞，而无需进行基因改造。我们通过体外操作初级卵泡和早期次级卵泡成功获得了自体鼠干细胞，并且该方法已证明即使对于从老龄卵巢中获取的卵泡也能成功。此外，我们认为直接从非生殖系卵巢组织中分离干细胞或通过将卵巢细胞与其他体细胞共同培养来获得干细胞将是可行的。如果实现这些目标，将极大地推动诱导多能干细胞技术以及组织特异性干细胞研究的发展。在本综述中，我们介绍了从卵巢组织细胞中建立无基因操作的组织相容性干细胞的相关技术，并综述了干细胞生物学当前的局限性和未来的研究方向。
