Differentiation Capacity of Human Urine-Derived Stem Cells to Retain Telomerase Activity.
Differentiation Capacity of Human Urine-Derived Stem Cells to Retain Telomerase Activity.
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DOI：
10.3389/fcell.2022.890574
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发表时间：
2022
影响因子：
5.5
通讯作者：
Zhang, Yuanyuan
中科院分区：
文献类型：
--
作者：
Shi, Yingai;Liu, Guihua;Wu, Rongpei;Mack, David L.;Sun, Xiuzhi Susan;Maxwell, Joshua;Guan, Xuan;Atala, Anthony;Zhang, Yuanyuan
端粒酶活性对于胚胎干细胞、诱导多能干细胞和癌症干细胞以及一些成体干细胞（例如人尿源干细胞 (USC)）的自我更新和潜力至关重要。然而，目前尚不清楚端粒酶活性如何影响成体干细胞的再生潜力。本研究的目的是确定端粒酶活性的再生意义，特别是在人原代 USC 的每个克隆群体中保留细胞表面标志物表达、多能分化能力、染色体稳定性和体内致瘤转化。总共从 10 名健康男性成年人（25-57 岁）身上获得了 117 份 USC 样本。使用端粒重复序列的聚合酶链式反应扩增来检测具有阳性端粒酶活性的 USC (USCsTA+)。从 117 个 USC 克隆中总共鉴定出 80 个 USCsTA+ (70.2%)，但在配对的正常膀胱平滑肌细胞和骨髓基质细胞样本中未检测到它们。在 20-40 岁年龄组中，大约 75% 的 USC 克隆表现出阳性端粒酶活性，而在 50 岁年龄组中，59.2% 的 USC 克隆表现出阳性端粒酶活性。与 USCsTA− 相比，USCsTA+ 延伸至第 16 代，经历了 62.0 ± 4.8 群体倍增，产生了更多细胞，并且在成骨、肌源和尿上皮分化方面更优越。重要的是，USC在植入体内后显示出正常的染色体并且没有肿瘤转化。总体而言，作为一种安全的细胞来源，端粒酶阳性的 USC 在细胞增殖和多能分化能力方面具有强大的再生潜力。
Telomerase activity is essential for the self-renewal and potential of embryonic, induced pluripotent, and cancer stem cells, as well as a few somatic stem cells, such as human urine-derived stem cells (USCs). However, it remains unclear how telomerase activity affects the regeneration potential of somatic stem cells. The objective of this study was to determine the regenerative significance of telomerase activity, particularly to retain cell surface marker expression, multipotent differentiation capability, chromosomal stability, and in vivo tumorigenic transformation, in each clonal population of human primary USCs. In total, 117 USC specimens from 10 healthy male adults (25–57 years of age) were obtained. Polymerase chain reaction amplification of a telomeric repeat was used to detect USCs with positive telomerase activity (USCsTA+). A total of 80 USCsTA+ (70.2%) were identified from 117 USC clones, but they were not detected in the paired normal bladder smooth muscle cell and bone marrow stromal cell specimens. In the 20–40 years age group, approximately 75% of USC clones displayed positive telomerase activity, whereas in the 50 years age group, 59.2% of the USC clones expressed positive telomerase activity. USCsTA+ extended to passage 16, underwent 62.0 ± 4.8 population doublings, produced more cells, and were superior for osteogenic, myogenic, and uroepithelial differentiation compared to USCsTA−. Importantly, USCs displayed normal chromosome and no oncological transformation after being implanted in vivo. Overall, as a safe cell source, telomerase-positive USCs have a robust regenerative potential in cell proliferation and multipotent differentiation capacity.
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