Abstract
Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.
概要
体外培养扩增的间充质干细胞 (MSCs) 因具有愈合损伤组织的能力而被研究. MSCs 的移植可促进受损组织的修复, 并且能分化为目标细胞或是对存活的目的细胞起保护作用. 但目前 MSCs 的移植修复效率受限于被移植到目标区域后, MSCs 的存活率低. 因此, 现在迫切需要制定提高 MSCs 修复效率的策略. 铁含量过载、 活性氧蓄积以及抗氧化性能的下降均会抑制 MSCs 的增殖和再生能力, 从而加速 MSCs 的死亡过程. 值得注意的是, 铁离子含量过载引发的氧化应激 (OS) 及伴随其后的抗氧化系统失衡是铁死亡发生的经典通路. 因此我们认为, 铁死亡通路可能抑制 MSCs 移植后的细胞存活, 降低了 MSCs 的修复疗效. 在本综述中, 我们探讨了 MSCs 中的铁死亡通路. 鉴于目前 MSCs 中铁死亡的相关研究不足, 迫切需要进一步研究, 以期提高 MSCs 在体内的移植修复效率.
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This work was supported by the Jiangsu Provincial Natural Science Foundation of China (No. BK20220832).
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Yuzhu XU and Yuntao WANG designed the manuscript. Yuzhu XU, Pan FAN, and Yuntao WANG wrote the manuscript. Yuzhu XU, Lei LIU, Xuanfei XU, Lele ZHANG, and Xiaolong LI provided opinions. Yuzhu XU, Jiadong WANG, Yuao TAO, and Xi LI were involved in the discussion. All authors have read and approved the final manuscript.
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Yuzhu XU, Pan FAN, Lei LIU, Xuanfei XU, Lele ZHANG, Jiadong WANG, Yuao TAO, Xiaolong LI, Xi LI, and Yuntao WANG declare that they have no conflict of interest.
This review does not contain any studies with human or animal subjects performed by any of the authors.
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Xu, Y., Fan, P., Liu, L. et al. Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway. J. Zhejiang Univ. Sci. B 24, 115–129 (2023). https://doi.org/10.1631/jzus.B2200410
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DOI: https://doi.org/10.1631/jzus.B2200410
Key words
- Mesenchymal stem cells (MSCs)
- Ferroptosis
- Oxidative stress (OS)
- Iron metabolism
- Lipid peroxidation
- Glutathione peroxidase 4 (GPX4)