Lee Won-Cheol, Kim Dae-Young, Kim Mi-Jeong, Lee Hyeon-Jeong, Bharti Dinesh, Lee Sung-Ho, Kang Young-Hoon, Rho Gyu-Jin, Jeon Byeong-Gyun
Department of Biology Education, Gyeongsang National University, Jinju, Republic of Korea.
OBS/Theriogenology and Biotechnology, Gyeongsang National University, Jinju, Republic of Korea.
Anim Cells Syst (Seoul). 2019 Aug 13;23(5):335-345. doi: 10.1080/19768354.2019.1651767. eCollection 2019.
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 ( < .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 ( < .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 ( < .05) increased, while positive surface markers for MSCs, such as CD90 and CD105, were significantly ( < .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 ( < .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.
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(DSCs)的细胞特性。在DSCs长时间暴露2周后,与未处理的DSCs相比,用250和500 μM NVP处理的DSCs中,细胞群体倍增时间(PDT)因细胞生长延迟而显著(<0.05)增加。此外,与未处理的DSCs相比,在250 μM NVP处理的DSCs中,具有高衰老相关β-半乳糖苷酶活性的细胞周期G1期也显著(<0.05)增加。对照组和处理组之间端粒酶活性水平没有变化。然而,在NVP处理后,与未处理的DSCs相比,间充质干细胞(MSCs)的阴性表面标志物如CD34和CD45在NVP处理的DSCs中显著(<0.05)增加,而MSCs的阳性表面标志物如CD90和CD105则显著(<0.05)减少。此外,向中胚层谱系的分化能力逐渐降低,与未处理的对照DSCs相比,在NVP处理的DSCs中观察到NANOG、OCT-4和SOX-2转录本的表达水平显著(<0.05)降低。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。