iPSCs-derived mesenchymal stromal cells mitigate anxiety and neuroinflammation in aging female mice.
iPSCs-derived mesenchymal stromal cells mitigate anxiety and neuroinflammation in aging female mice.
复制标题
DOI：
10.1016/j.biocel.2022.106347
复制
发表时间：
2022-12
期刊：
影响因子：
--
通讯作者：
Xiaoyue Wei;Ruijie Li;Xiangyu Li;Boyan Wang;Jianyang Huang;Han-Lu Mu;Qinmu Zhang;Ziyuan Zhang;Yifei Ru;Xinxiang Wu;Y. Qiu;Yan-Chen Ye;Yuanyuan Feng;Shiyu Wang;Hui Chen;Chenju Yi;Jiancheng Wang
中科院分区：
文献类型：
--
作者：
Xiaoyue Wei;Ruijie Li;Xiangyu Li;Boyan Wang;Jianyang Huang;Han-Lu Mu;Qinmu Zhang;Ziyuan Zhang;Yifei Ru;Xinxiang Wu;Y. Qiu;Yan-Chen Ye;Yuanyuan Feng;Shiyu Wang;Hui Chen;Chenju Yi;Jiancheng Wang
围绝经期是向更年期的自然过渡，荷尔蒙紊乱会导致短期的精神障碍，如焦虑，以及由于血脑屏障(BBB)受损而导致的长期神经炎，这可能会导致更严重的神经疾病，如痴呆症。有效的治疗可以预防短期和长期的神经后遗症，这构成了本研究的目的。取16~18月龄雌性C57BL/6小鼠，经尾静脉注射人诱导多能干细胞(IPSCs)分化而来的间充质基质细胞(MSCs)。小鼠的血液雌激素水平增加，焦虑和神经炎症减轻，血脑屏障完整性改善。有趣的是，移植的MSCs靠近卵巢交感神经，降低了卵巢去甲肾上腺素水平，进而增加了卵巢雌激素的分泌。此外，给予雌激素合成抑制剂阿那曲唑降低了MSCs在体内的治疗效果，提示这种作用是雌激素依赖的。体外研究证实了MSCs通过线粒体交换对交感神经的影响。总之，IPSC来源的MSCs可能提供了一种新的选择来管理围绝经期相关的激素失调和女性衰老过程中的神经疾病。
Perimenopause is a natural transition to menopause, when hormone disturbance can result in both short-term mental disorders, such as anxiety, and long-term neuroinflammation due to blood-brain barrier (BBB) impairment, which may lead to more serious neurological disorders later on, such as dementia. Effective treatments may prevent both short-term and long-term neurological sequela, which formed the aim of this study. In aged female C57BL/6 mice (16–18 months of age), mesenchymal stromal cells (MSCs) differentiated from human-induced pluripotent stem cells (iPSCs), were administered via tail vein injection. Mice showed increased blood estrogen levels, alleviated anxiety and neuroinflammation, and improved BBB integrity. Interestingly, transplanted MSCs were located close to ovarian sympathetic nerves and decreased ovarian norepinephrine levels, which in turn increased ovarian estrogen secretion. Moreover, the administration of anastrozole, an inhibitor of estrogen synthesis, diminished the therapeutic effects of MSCsin vivo, suggesting the effect to be estrogen-dependent.In vitrostudy confirmed the impact of MSCs on sympathetic nerves via mitochondria exchange. In conclusion, iPSC-derived MSCs may provide a novel option to manage perimenopause-related hormonal dysregulation and neurological disorders during the female aging process.