Germline niche transplantation restores fertility in infertile mice
Germline niche transplantation restores fertility in infertile mice
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DOI：
10.1093/humrep/dei096
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发表时间：
2005-09-01
影响因子：
6.1
通讯作者：
Shinohara, T
中科院分区：
文献类型：
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作者：
Kanatsu-Shinohara, M;Miki, H;Shinohara, T
背景：干细胞与其微环境或生态位密切相关，生态位异常会危及自我更新的组织。例如，在睾丸中，支持细胞与生殖细胞相互作用，支持细胞的缺陷会影响精子发生，导致男性不育。方法和结果：将来自不育白色斑点（W）小鼠的健康支持细胞移植到具有缺陷支持细胞的不育Steel（SI）小鼠睾丸的曲细精管中，在受体睾丸中从SI干细胞发生精子发生。平均而言，1.1%的受体小管显示精子发生。此外，在睾丸中发育的生殖细胞的显微授精实验中，我们从114个成功注射的卵母细胞中获得了4个正常的后代。结论：本研究表明，男性种系微环境的缺陷可以通过支持细胞移植来纠正。尽管需要进一步改进以提高精子发生的低效率，但通过生态位移植纠正环境缺陷的能力对于开发治疗自我更新组织中无法治愈的疾病的新策略具有重要意义。
BACKGROUND: Stem cells interact closely with their microenvironment or niche, and abnormalities in niche compromise the self-renewing tissue. In testis, for example, Sertoli cells interact with germ cells, and defects in Sertoli cells compromises spermatogenesis, leading to male infertility. However, it has not been possible to restore spermatogenesis from endogenous stem cells in infertile testis with environmental defects METHODS AND RESULTS: When healthy Sertoli cells from infertile white spotting (W) mouse were transplanted into the seminiferous tubules of infertile Steel (SI) mouse testis that had defective Sertoli cells, spermatogenesis occurred from SI stem cells in the recipient testis. On average, 1.1% of the recipient tubules showed spermatogenesis. Furthermore, in a microinsemination experiment with germ cells that developed in the testis, we obtained four normal offspring from 114 successfully injected oocytes. CONCLUSIONS: This study demonstrates that defects in male germline microenvironment can be corrected by Sertoli cell transplantation. Although further improvements are required to enhance the low efficiency of spermatogenesis, the ability to correct environmental defect by niche transplantation has important implications in developing new strategies for treating incurable disorders in self-renewing tissues.