Rationale: Stem cell-based therapies have emerged as promising tools for tissue engineering and regenerative medicine, but their therapeutic efficacy is largely limited by the oxidative stress-induced loss of transplanted cells at injured tissue sites. To address this issue, we aimed to explore the underlying mechanism and protective strategy of ROS-induced MSC loss./nMethods: Changes in TFAM (mitochondrial transcription factor A) signaling, mitochondrial function, DNA damage, apoptosis and senescence in MSCs under oxidative stress conditions were assessed using real-time PCR, western blotting and RNA sequencing, etc. The impact of TFAM or lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) knockdown or overexpression on mitochondrial function, DNA damage repair, apoptosis and senescence in MSCs was also analyzed. The effect of mitochondrion-targeted antioxidant (Mito-TEMPO) on the survival of transplanted MSCs was evaluated in a mouse model of renal ischemia/reperfusion (I/R) injury./nResults: Mitochondrial ROS (mtROS) bursts caused defects in TFAM signaling and overall mitochondrial function, which further impaired NEAT1 expression and its mediated paraspeckle formation and DNA repair pathways in MSCs, thereby jointly promoting MSC senescence and death under oxidative stress. In contrast, targeted inhibition of the mtROS bursts is a sufficient strategy for attenuating early transplanted MSC loss at injured tissue sites, and coadministration of Mito-TEMPO improved the local retention of transplanted MSCs and reduced oxidative injury in ischemic kidneys./nConclusions: This study identified the critical role of the mitochondria‒paraspeckle axis in regulating cell survival and may provide insights into developing advanced stem cell therapies for tissue engineering and regenerative medicine.

中文翻译：

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线粒体旁斑轴调节氧化应激条件下移植干细胞的存活

理由：基于干细胞的疗法已成为组织工程和再生医学的有前途的工具，但其治疗效果在很大程度上受到氧化应激引起的受损组织部位移植细胞损失的限制。为了解决这个问题，我们旨在探讨ROS诱导的MSC损失的潜在机制和保护策略。/n方法：氧化作用下MSCs中TFAM（线粒体转录因子A）信号、线粒体功能、DNA损伤、凋亡和衰老的变化采用实时PCR、蛋白质印迹和RNA测序等方法评估应激条件。还研究了TFAM或lncRNA核副斑组装转录物1（NEAT1）敲低或过表达对MSCs线粒体功能、DNA损伤修复、细胞凋亡和衰老的影响。分析了。在肾缺血/再灌注 (I/R) 损伤小鼠模型中评估了线粒体靶向抗氧化剂 (Mito-TEMPO) 对移植的 MSC 存活的影响。/n结果：线粒体 ROS (mtROS) 爆发导致 TFAM 缺陷信号传导和整体线粒体功能，进一步损害 MSC 中的 NEAT1 表达及其介导的旁斑形成和 DNA 修复途径，从而共同促进氧化应激下 MSC 的衰老和死亡。相比之下，靶向抑制 mtROS 爆发是减轻受损组织部位早期移植 MSC 损失的充分策略，并且 Mito-TEMPO 的共同给药改善了移植 MSC 的局部保留并减少了缺血肾脏中的氧化损伤。/n 结论：这研究确定了线粒体旁斑轴在调节细胞存活中的关键作用，并可能为开发用于组织工程和再生医学的先进干细胞疗法提供见解。