Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells.

IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING
Qi-Ming Huang, You-Qiong Zhuo, Zhong-Xin Duan, Yin-Lin Long, Jia-Nan Wang, Zhou-Hang Zhang, Shao-Yong Fan, Yong-Ming Huang, Ke-Yu Deng, Hong-Bo Xin
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引用次数: 0

Abstract

Aims: Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application.

Methods: In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II.

Results: We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13).

Conclusion: Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function.

长期缺氧环境提高人脐带间充质干细胞的干性、免疫调节功能和治疗应用。
目的:间充质干细胞(Mesenchymal stem cells, MSCs)通常在体外常氧环境(21%)下培养,而在体内移植时,人体组织和器官中的氧浓度为1% ~ 10%。然而,缺氧对间充质干细胞的影响尚未深入研究,特别是其转化应用。方法:在本研究中,我们研究了人脐带来源的间充质干细胞(hUC-MSCs)分别在低氧(1%)和常氧(21%)环境下从初级培养到30代的长期培养特性。两种气氛的比较系统分析了MSCs的生物学功能,主要包括干细胞维持、免疫调节和对软骨细胞凋亡的抵抗,并研究了其在胶原酶II构建的骨关节炎(OA)大鼠中的关节功能和抗炎作用。结果:我们观察到hUC-MSCs培养过程中,长期缺氧培养在促进增殖、抗致瘤性、维持正常核型和干性、抑制衰老、提高软骨细胞免疫调节功能和抗凋亡作用等方面优于常温培养。此外,我们证明长期缺氧hUC-MSCs (Hy-MSCs)移植对OA大鼠的治疗效果优于常温培养hUC-MSCs (No-MSCs),在改善关节功能和肿胀恢复方面,并显著抑制促炎因子的分泌,通过降低基质金属肽酶13 (MMP-13)的表达,有效减轻软骨损伤。结论:Hy-MSCs通过促进干细胞维持和增强免疫调节功能,具有巨大的临床应用潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bone & Joint Research
Bone & Joint Research CELL & TISSUE ENGINEERING-ORTHOPEDICS
CiteScore
7.40
自引率
23.90%
发文量
156
审稿时长
12 weeks
期刊介绍: The gold open access journal for the musculoskeletal sciences. Included in PubMed and available in PubMed Central.
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