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Age-related alteration in characteristics, function, and transcription features of ADSCs
Stem Cell Research & Therapy ( IF 7.5 ) Pub Date : 2021-08-23 , DOI: 10.1186/s13287-021-02509-0
Keya Li 1 , Guiying Shi 1 , Xuepei Lei 1 , Yiying Huang 1 , Xinyue Li 1 , Lin Bai 1 , Chuan Qin 1
Affiliation  

Adipose tissue-derived stem cells (ADSCs) autologous transplantation has been a promising strategy for aging-related disorders. However, the relationship between ADSCs senescence and organismal aging has not been clearly established. Therefore, we aimed at evaluating senescence properties of ADSCs from different age donors and to verify the influence of organismal aging on the proliferation and function of ADSCs in vitro, providing the theoretical basis for the clinical application of autologous ADSCs transplantation. The ADSCs were obtained from 1-month-old and 20-month-old mice. The cells characteristics, functions, gene expression levels, apoptosis proportion, cell cycle, SA-β-gal staining, and transcription features were evaluated. Compared to ADSCs from 1-month-old mice, ADSCs from 20-month-old mice exhibited some senescence-associated changes, including inhibited abilities to proliferate. Moreover, differentiation abilities, cell surface markers, and cytokines secreting differed between 1M and 20M ADSCs. SA-β-Gal staining did not reveal differences between the two donor groups, while cells exhibited more remarkable age-related changes through continuous passages. Based on transcriptome analysis and further detection, the CCL7-CCL2-CCR2 axis is the most probable mechanism for the differences. ADSCs from old donors have some age-related alterations. The CCL7-CCL2-CCR2 axis is a potential target for gene therapy to reduce the harmful effects of ADSCs from old donors. To improve on autologous transplantation, we would recommend that ADSCs should be cryopreserved in youth with a minimum number of passages or block CCL7-CCL2-CCR2 to abolish the effects of age-related alterations in ADSCs through the Chemokine signaling pathway.

中文翻译:

ADSCs 特征、功能和转录特征的年龄相关改变

脂肪组织来源的干细胞 (ADSCs) 自体移植已成为治疗衰老相关疾病的一种很有前景的策略。然而,ADSCs衰老与机体衰老之间的关系尚未明确。因此,我们旨在评估不同年龄供体ADSCs的衰老特性,并在体外验证机体衰老对ADSCs增殖和功能的影响,为自体ADSCs移植的临床应用提供理论依据。ADSCs 取自 1 个月大和 20 个月大的小鼠。评估细胞特征、功能、基因表达水平、凋亡比例、细胞周期、SA-β-gal 染色和转录特征。与 1 个月大小鼠的 ADSC 相比,来自 20 个月大小鼠的 ADSC 表现出一些与衰老相关的变化,包括增殖能力受到抑制。此外,1M 和 20M ADSCs 的分化能力、细胞表面标志物和细胞因子分泌不同。SA-β-Gal 染色未显示两个供体组之间的差异,而细胞通过连续传代表现出更显着的年龄相关变化。基于转录组分析和进一步检测,CCL7-CCL2-CCR2 轴是差异的最可能机制。来自老年捐赠者的 ADSCs 有一些与年龄相关的改变。CCL7-CCL2-CCR2 轴是基因治疗的潜在目标,以减少来自老年供体的 ADSCs 的有害影响。为了改善自体移植,
更新日期:2021-08-24
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