Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice.
Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice.
复制标题
INK128 抑制 Mtor 可延长衰老和早衰小鼠生殖系干细胞重建卵巢的功能
作者：
Heng D;Sheng X;Tian C;Li J;Liu L;Gou M;Liu L
干细胞移植已被普遍认为是有前途的治疗方法，在保存或恢复功能的损失，损坏，或老化的组织。原始生殖细胞（PGCs）或卵原细胞干细胞（OSCs）移植可重建卵巢功能，但维持时间较短，限制了干细胞在保持生育力和内分泌功能方面的潜在应用。在这里，我们表明INK 128对mTOR的抑制延长了PGCs/OSC移植后衰老和早衰小鼠中重建卵巢的卵泡和内分泌功能。通过将PGC移植到受体小鼠的肾被膜中而重建的卵巢的卵泡发育和内分泌功能通过INK 128处理维持超过12周，与之形成对比的是，对照仅维持约4周而不接受mTOR抑制剂。相对而言，雷帕霉素也能延长卵巢功能，但时间有限。此外，我们的数据显示，INK 128除了其已知的抑制免疫应答和炎症的功能外，还促进线粒体功能。总之，生殖系干细胞移植联合INK 128对mTOR的抑制改善并延长了生殖衰老和早衰小鼠的重建卵巢和内分泌功能。
Stem cell transplantation has been generally considered as promising therapeutics in preserving or recovering functions of lost, damaged, or aging tissues. Transplantation of primordial germ cells (PGCs) or oogonia stem cells (OSCs) can reconstitute ovarian functions that yet sustain for only short period of time, limiting potential application of stem cells in preservation of fertility and endocrine function. Here, we show that mTOR inhibition by INK128 extends the follicular and endocrine functions of the reconstituted ovaries in aging and premature aging mice following transplantation of PGCs/OSCs. Follicular development and endocrine functions of the reconstituted ovaries by transplanting PGCs into kidney capsule of the recipient mice were maintained by INK128 treatment for more than 12 weeks, in contrast to the controls for only about 4 weeks without receiving the mTOR inhibitors. Comparatively, rapamycin also can prolong the ovarian functions but for limited time. Furthermore, our data reveal that INK128 promotes mitochondrial function in addition to its known function in suppression of immune response and inflammation. Taken together, germline stem cell transplantation in combination with mTOR inhibition by INK128 improves and extends the reconstituted ovarian and endocrine functions in reproductive aging and premature aging mice.
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影响因子：
56.9
作者：
de Morree, Antoine;Klein, Julian D. D.;Rando, Thomas A.
通讯作者：
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影响因子：
23.9
作者：
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DOI：
10.1073/pnas.1800352115
发表时间：
2018-06-05
影响因子：
11.1
作者：
Guo J;Zhang T;Guo Y;Sun T;Li H;Zhang X;Yin H;Cao G;Yin Y;Wang H;Shi L;Guo X;Sha J;Eppig JJ;Su YQ
通讯作者：
Su YQ