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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway

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.

Key words: Mesenchymal stem cells (MSCs); Ferroptosis; Oxidative stress (OS); Iron metabolism; Lipid peroxidation; Glutathione peroxidase 4 (GPX4)

Chinese Summary  <298> 间充质干细胞移植治疗的新视角:靶向铁死亡通路

徐玉柱1,2,樊攀1,2,刘磊1,2,徐玄飞3,张乐乐1,2,王佳东1,2,陶禹澳1,2,李骁龙1,2,李熹1,2,王运涛1,2
1东南大学医学院,中国南京市,210009
2东南大学附属中大医院脊柱外科中心,中国南京市,210009
3东南大学附属中大医院核医学科,中国南京市,210009
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。

关键词组:间充质干细胞(MSCs);铁死亡;氧化应激(OS);铁代谢途径;脂质过氧化; 谷胱甘肽过氧化物酶4(GPX4)


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DOI:

10.1631/jzus.B2200410

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On-line Access:

2023-02-05

Received:

2022-08-21

Revision Accepted:

2022-10-26

Crosschecked:

2023-02-09

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