Human umbilical cord mesenchymal stem cell-derived exosome ameliorate doxorubicin-induced senescence

IF 3.3 3区生物学 Q3 CELL BIOLOGY Experimental cell research Pub Date : 2025-02-21 DOI:10.1016/j.yexcr.2025.114450

Zhen Yang , Feng Yan , Jiangwei Yuan , Manjun Yang , Jinyu Wang , Changqiao You , Kaiqun Ren

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Abstract

Background

Cellular senescence refers to a condition where cells permanently cease division while maintaining metabolic activity. Doxorubicin (Dox) is known as an agent of induction of cellular senescence. This study aimed to explore the potential role of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) in mitigating Dox induced senescent.

Method

NIH3T3 cells were treated by various concentrations of Dox with or without hucMSC-Exo, cell morphology, viability, migration, senescence-associated SA-β-Gal staining were monitored. Cellular senescence was induced in C57BL/6J mice via administration of 5 mg/kg Doxorubicin, followed by treatment with hucMSC-Exo or metformin. Assessments included body weight, liver and kidney weight, colon length, SA-β-Gal staining of kidney and skin, molecular biomarkers of aging such as p16^INK4A, p53, and p21^Waf1/Clip1 to evaluate senescence status.

Result

We found that after the treatment of exosomes or metformin improved several aging-related phenotypes in both mouse and cellular models, including increases in body weight, liver and kidney weights, and the reduction of SA-β-Gal positive cells in kidney and skin tissues as well as cell models. At the molecular level, hucMSC-Exo resulted in the downregulation of inflammatory factors and senescence markers in liver and kidney tissues as well as cell models.

Conclusion

Our study demonstrates hucMSC-Exo may ameliorate Dox induced senescence either in NIH3T3 cells or in mice.

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背景：细胞衰老是指细胞在保持新陈代谢活动的同时永久停止分裂的一种状态。众所周知，多柔比星（Dox）是诱导细胞衰老的一种药物。本研究旨在探索人脐带间充质干细胞衍生的外泌体（hucMSC-Exo）在缓解Dox诱导的衰老中的潜在作用：方法：用不同浓度的Dox处理NIH3T3细胞，加入或不加入hucMSC-Exo，监测细胞形态、活力、迁移、衰老相关的SA-β-Gal染色。给 C57BL/6J 小鼠注射 5 mg/kg 多柔比星，然后用 hucMSC-Exo 或二甲双胍处理，诱导细胞衰老。评估包括体重、肝脏和肾脏重量、结肠长度、肾脏和皮肤的 SA-β-Gal 染色、衰老的分子生物标志物（如 p16INK4A、p53 和 p21Waf1/Clip1），以评估衰老状态：结果：我们发现，外泌体或二甲双胍处理后，小鼠和细胞模型中与衰老相关的几种表型都得到了改善，包括体重、肝脏和肾脏重量的增加，肾脏、皮肤组织和细胞模型中SA-β-Gal阳性细胞的减少。在分子水平上，hucMSC-Exo导致肝脏和肾脏组织以及细胞模型中的炎症因子和衰老标志物下调：我们的研究表明，hucMSC-Exo 可改善 NIH3T3 细胞或小鼠中由 Dox 引起的衰老。

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.