MSC-mediated mitochondrial transfer promotes metabolic reprograming in endothelial cells and vascular regeneration in ARDS.

IF 5.2 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Report Pub Date : 2025-12-01 Epub Date: 2025-03-13 DOI:10.1080/13510002.2025.2474897

Jinlong Wang, Shanshan Meng, Yixuan Chen, Haofei Wang, Wenhan Hu, Shuai Liu, Lili Huang, Jingyuan Xu, Qing Li, Xiaojing Wu, Wei Huang, Yingzi Huang

{"title":"MSC-mediated mitochondrial transfer promotes metabolic reprograming in endothelial cells and vascular regeneration in ARDS.","authors":"Jinlong Wang, Shanshan Meng, Yixuan Chen, Haofei Wang, Wenhan Hu, Shuai Liu, Lili Huang, Jingyuan Xu, Qing Li, Xiaojing Wu, Wei Huang, Yingzi Huang","doi":"10.1080/13510002.2025.2474897","DOIUrl":null,"url":null,"abstract":"Background: Mesenchymal stem cells (MSCs) are a potential therapy for acute respiratory distress syndrome (ARDS), but their mechanisms in repairing mitochondrial damage in ARDS endothelial cells remain unclear.Methods: We first examined MSCs' mitochondrial transfer ability and mechanisms to mouse pulmonary microvascular endothelial cells (MPMECs) in ARDS. Then, we investigated how MSC-mediated mitochondrial transfer affects the repair of endothelial damage. Finally, we elucidated the mechanisms by which MSC-mediated mitochondrial transfer promotes vascular regeneration.Results: Compared to mitochondrial-damaged MSCs, normal MSCs showed a significantly higher mitochondrial transfer rate to MPMECs, with increases of 41.68% in vitro (P < 0.0001) and 10.50% in vivo (P = 0.0005). Furthermore, MSC-mediated mitochondrial transfer significantly reduced reactive oxygen species (P < 0.05) and promoted proliferation (P < 0.0001) in MPMECs. Finally, MSC-mediated mitochondrial transfer significantly increased the activity of the tricarboxylic acid (TCA) cycle (MD of CS mRNA: 23.76, P = 0.032), and further enhanced fatty acid synthesis (MD of FAS mRNA: 6.67, P = 0.0001), leading to a 6.7-fold increase in vascular endothelial growth factor release from MPMECs and promoted vascular regeneration in ARDS.Conclusion: MSC-mediated mitochondrial transfer to MPMECs activates the TCA cycle and fatty acid synthesis, promoting endothelial proliferation and pro-angiogenic factor release, thereby enhancing vascular regeneration in ARDS.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2474897"},"PeriodicalIF":5.2000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912292/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Redox Report","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/13510002.2025.2474897","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Mesenchymal stem cells (MSCs) are a potential therapy for acute respiratory distress syndrome (ARDS), but their mechanisms in repairing mitochondrial damage in ARDS endothelial cells remain unclear.

Methods: We first examined MSCs' mitochondrial transfer ability and mechanisms to mouse pulmonary microvascular endothelial cells (MPMECs) in ARDS. Then, we investigated how MSC-mediated mitochondrial transfer affects the repair of endothelial damage. Finally, we elucidated the mechanisms by which MSC-mediated mitochondrial transfer promotes vascular regeneration.

Results: Compared to mitochondrial-damaged MSCs, normal MSCs showed a significantly higher mitochondrial transfer rate to MPMECs, with increases of 41.68% in vitro (P < 0.0001) and 10.50% in vivo (P = 0.0005). Furthermore, MSC-mediated mitochondrial transfer significantly reduced reactive oxygen species (P < 0.05) and promoted proliferation (P < 0.0001) in MPMECs. Finally, MSC-mediated mitochondrial transfer significantly increased the activity of the tricarboxylic acid (TCA) cycle (MD of CS mRNA: 23.76, P = 0.032), and further enhanced fatty acid synthesis (MD of FAS mRNA: 6.67, P = 0.0001), leading to a 6.7-fold increase in vascular endothelial growth factor release from MPMECs and promoted vascular regeneration in ARDS.

Conclusion: MSC-mediated mitochondrial transfer to MPMECs activates the TCA cycle and fatty acid synthesis, promoting endothelial proliferation and pro-angiogenic factor release, thereby enhancing vascular regeneration in ARDS.

查看原文本刊更多论文

间质干细胞介导的线粒体转移促进ARDS内皮细胞的代谢重编程和血管再生。

背景：间充质干细胞（MSCs）是急性呼吸窘迫综合征（ARDS）的潜在治疗方法，但其修复ARDS内皮细胞线粒体损伤的机制尚不清楚。方法：我们首先检测骨髓间充质干细胞向ARDS小鼠肺微血管内皮细胞（MPMECs）的线粒体转移能力及其机制。然后，我们研究了msc介导的线粒体转移如何影响内皮损伤的修复。最后，我们阐明了msc介导的线粒体转移促进血管再生的机制。结果：与线粒体损伤的MSCs相比，正常MSCs向mpmec的线粒体转移率显著提高，体外升高41.68% （P = 0.0005）。此外，msc介导的线粒体转移显著降低了活性氧（P P P = 0.032），并进一步增强了脂肪酸合成（FAS mRNA的MD: 6.67, P = 0.0001），导致血管内皮生长因子释放增加6.7倍，促进了ARDS血管再生。结论：msc介导的线粒体向mpmes转移激活了TCA循环和脂肪酸合成，促进了内皮细胞增殖和促血管生成因子的释放，从而促进了ARDS血管再生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Redox Report 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.