ABSTRACT The present study investigated the cellular properties in the dental tissue-derived mesenchymal stem cells (DSCs) exposed to nevirapine (NVP), an inhibitor of reverse transcriptase (RTase). After a prolonged exposure of DSCs for 2 weeks, the population doubling time (PDT) was significantly (P < .05) increased by delayed cell growth in the DSCs treated with 250 and 500 μM NVP, compared with untreated DSCs. Furthermore, the G1 phase of cell cycle with high activity of senescence-associated β-galactosidase was also significantly (P < .05) increased in the 250 μM NVP-treated DSCs, compared with untreated DSCs. The level of telomerase activity was unchanged between control and treatment. However, following the treatment of NVP, negative surface markers for mesenchymal stem cells (MSCs), such as CD34 and CD45, were significantly (P < .05) increased, while positive surface markers for MSCs, such as CD90 and CD105, were significantly (P < .05) decreased in the NVP-treated DSCs than those of untreated DSCs. Furthermore, the differentiation capacity into mesodermal lineage was gradually decreased, and a significant (P < .05) decrease of expression level of NANOG, OCT-4 and SOX-2 transcripts was observed in the DSCs treated with NVP, compared with untreated control DSCs. Taken together, the present results have revealed that inhibition of RTase by NVP induces delayed cell growth and loss of stemness.

中文翻译：

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通过抑制源自牙齿组织的人类间充质干细胞的逆转录来延迟细胞生长和干性丧失

摘要 本研究调查了暴露于逆转录酶 (RTase) 抑制剂奈韦拉平 (NVP) 的牙组织来源间充质干细胞 (DSC) 的细胞特性。在 DSC 长时间暴露 2 周后，与未处理的 DSC 相比，在 250 和 500 μM NVP 处理的 DSC 中，由于细胞生长延迟，群体倍增时间 (PDT) 显着增加（P < .05）。此外，与未处理的 DSC 相比，在 250 μM NVP 处理的 DSC 中，具有高活性的衰老相关 β-半乳糖苷酶的细胞周期 G1 期也显着增加（P < .05）。端粒酶活性水平在对照和处理之间没有变化。然而，在 NVP 治疗后，间充质干细胞 (MSC) 的阴性表面标志物，如 CD34 和 CD45，显着（P < . 05) 增加，而 MSC 的阳性表面标志物，如 CD90 和 CD105，在 NVP 处理的 DSC 中比未处理的 DSC 显着降低 (P < .05)。此外，向中胚层谱系的分化能力逐渐降低，与未处理的对照 DSC 相比，在 NVP 处理的 DSC 中观察到 NANOG、OCT-4 和 SOX-2 转录物的表达水平显着降低（P < .05） . 综上所述，目前的结果表明，NVP 对 RTase 的抑制会导致细胞生长延迟和干性丧失。与未处理的对照 DSC 相比，在 NVP 处理的 DSC 中观察到 NANOG、OCT-4 和 SOX-2 转录物的表达水平显着降低（P < .05）。综上所述，目前的结果表明，NVP 对 RTase 的抑制会导致细胞生长延迟和干性丧失。与未处理的对照 DSC 相比，在 NVP 处理的 DSC 中观察到 NANOG、OCT-4 和 SOX-2 转录物的表达水平显着降低（P < .05）。综上所述，目前的结果表明，NVP 对 RTase 的抑制会导致细胞生长延迟和干性丧失。