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Theranostics 2024; 14(4):1517-1533. doi:10.7150/thno.88764 This issue Cite

Research Paper

The mitochondria‒paraspeckle axis regulates the survival of transplanted stem cells under oxidative stress conditions

Meng Zhao1,2, Shuyun Liu1, Yizhuo Wang1, Ke Lv1, Peng Lou1, Pingya Zhou1, Jiaying Zhu2, Lan Li1, Jingqiu Cheng1, Yanrong Lu1, Jingping Liu1✉

1. Department of General Surgery and NHC Key Laboratory of Transplant Engineering and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
2. Department of Emergency, Guizhou Provincial People's Hospital, Guiyang 550002, China.

✉ Corresponding author: Jingping Liu; Address: NHC Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, No. 1 Keyuan 4th Road, Gaopeng Ave, Chengdu 610041, China; Tel: +86-28-85164029; Fax: +86-28-85164030; More

Citation:
Zhao M, Liu S, Wang Y, Lv K, Lou P, Zhou P, Zhu J, Li L, Cheng J, Lu Y, Liu J. The mitochondria‒paraspeckle axis regulates the survival of transplanted stem cells under oxidative stress conditions. Theranostics 2024; 14(4):1517-1533. doi:10.7150/thno.88764. https://www.thno.org/v14p1517.htm
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Abstract

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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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: mesenchymal stem cells, oxidative stress, mitochondria, paraspeckle, cell death

Citation styles

APA
Zhao, M., Liu, S., Wang, Y., Lv, K., Lou, P., Zhou, P., Zhu, J., Li, L., Cheng, J., Lu, Y., Liu, J. (2024). The mitochondria‒paraspeckle axis regulates the survival of transplanted stem cells under oxidative stress conditions. Theranostics, 14(4), 1517-1533. https://doi.org/10.7150/thno.88764.

ACS
Zhao, M.; Liu, S.; Wang, Y.; Lv, K.; Lou, P.; Zhou, P.; Zhu, J.; Li, L.; Cheng, J.; Lu, Y.; Liu, J. The mitochondria‒paraspeckle axis regulates the survival of transplanted stem cells under oxidative stress conditions. Theranostics 2024, 14 (4), 1517-1533. DOI: 10.7150/thno.88764.

NLM
Zhao M, Liu S, Wang Y, Lv K, Lou P, Zhou P, Zhu J, Li L, Cheng J, Lu Y, Liu J. The mitochondria‒paraspeckle axis regulates the survival of transplanted stem cells under oxidative stress conditions. Theranostics 2024; 14(4):1517-1533. doi:10.7150/thno.88764. https://www.thno.org/v14p1517.htm

CSE
Zhao M, Liu S, Wang Y, Lv K, Lou P, Zhou P, Zhu J, Li L, Cheng J, Lu Y, Liu J. 2024. The mitochondria‒paraspeckle axis regulates the survival of transplanted stem cells under oxidative stress conditions. Theranostics. 14(4):1517-1533.

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