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抗氧化剂可改善人脐带间充质干细胞对抗骨化性肌炎诱导的衰老的增殖能力及功效。

Antioxidants Improve the Proliferation and Efficacy of hUC-MSCs against HO-Induced Senescence.

作者信息

Zheng Zhaojuan, Wang Xia, Ouyang Liming, Chen Wenxia, Zhang Lixin, Cao Yulin

机构信息

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.

Beijing Tang Yi Hui Kang Biomedical Technology Co., Ltd., Beijing 100032, China.

出版信息

Antioxidants (Basel). 2023 Jun 24;12(7):1334. doi: 10.3390/antiox12071334.

DOI:10.3390/antiox12071334
PMID:37507874
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10376626/
Abstract

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are broadly applied in clinical treatment due to convenient accessibility, low immunogenicity, and the absence of any ethical issues involved. However, the microenvironment of inflammatory tissues may cause oxidative stress and induce senescence in transplanted hUC-MSCs, which will further reduce the proliferation, migration ability, and the final therapeutic effects of hUC-MSCs. Beta-nicotinamide mononucleotide (NMN) and coenzyme Q10 (CoQ10) are famous antioxidants and longevity medicines that could reduce intracellular reactive oxygen species levels by different mechanisms. In this study, hUC-MSCs were treated in vitro with NMN and CoQ10 to determine if they could reduce oxidative stress caused by hydrogen peroxide (HO) and recover cell functions. The effects of NMN and CoQ10 on the cell proliferation, the mRNA levels of the inflammatory cytokine and the anti-inflammatory cytokine , and the differentiation and cell migration ability of hUC-MSCs before and after HO treatment were investigated. The findings revealed that NMN and CoQ10 reduced HO-induced senescence and increased hUC-MSCs' proliferation in the late phase as passage 12 and later. The mRNA level of hUC-MSCs induced by HO was significantly decreased after antioxidant treatment. NMN and CoQ10 all reduced the adipogenic differentiation ability of hUC-MSCs. CoQ10 improved the chondrogenic differentiation ability of hUC-MSCs. Furthermore, NMN was found to significantly enhance the migration ability of hUC-MSCs. Transcriptomic analysis revealed that NMN and CoQ10 both increased DNA repair ability and cyclin expression and downregulated TNF and IL-17 inflammatory signaling pathways, thereby contributing to the proliferative promotion of senecent stem cells and resistance to oxidative stress. These findings suggest that antioxidants can improve the survival and efficacy of hUC-MSCs in stem cell therapy for inflammation-related diseases.

摘要

人脐带间充质干细胞（hUC-MSCs）因其易于获取、免疫原性低且不存在任何伦理问题而被广泛应用于临床治疗。然而，炎症组织的微环境可能会导致氧化应激并诱导移植的hUC-MSCs衰老，这将进一步降低hUC-MSCs的增殖、迁移能力以及最终的治疗效果。β-烟酰胺单核苷酸（NMN）和辅酶Q10（CoQ10）是著名的抗氧化剂和长寿药物，它们可以通过不同机制降低细胞内活性氧水平。在本研究中，hUC-MSCs在体外分别用NMN和CoQ10处理，以确定它们是否能减轻过氧化氢（HO）引起的氧化应激并恢复细胞功能。研究了NMN和CoQ10对HO处理前后hUC-MSCs的细胞增殖、炎性细胞因子和抗炎细胞因子的mRNA水平以及分化和细胞迁移能力的影响。研究结果显示，NMN和CoQ10减轻了HO诱导的衰老，并在第12代及以后的后期增加了hUC-MSCs的增殖。抗氧化剂处理后，HO诱导的hUC-MSCs的mRNA水平显著降低。NMN和CoQ10均降低了hUC-MSCs的成脂分化能力。CoQ10提高了hUC-MSCs的成软骨分化能力。此外，发现NMN能显著增强hUC-MSCs的迁移能力。转录组分析显示，NMN和CoQ10均提高了DNA修复能力和细胞周期蛋白表达，并下调了TNF和IL-17炎症信号通路，从而促进衰老干细胞的增殖并抵抗氧化应激。这些发现表明，抗氧化剂可以提高hUC-MSCs在炎症相关疾病干细胞治疗中的存活率和疗效。

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