Objective: 

Glioblastoma is one of the most lethal tumors in adult central nervous system with a median survival of a year and half and effective therapeutic strategy is urgently needed. For that reason, stem cell-based suicide gene therapies have attracted much interest because of potent tumor tropism of stem cells and bystander effect. In this current clinical situation, stem cells are promising delivery tool of suicide genes for glioma therapy. Since habitual cigarette smoking still prevails worldwide, we investigated the effect of nicotine on stem cell tropism toward glioma and gap junctional intercellular communication (GJIC) function between glioma and stem cells, both of which are important for suicide gene therapies. Methods: Mouse induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) and human dental pulp mesenchymal stem cells (DPSCs) were used. The effect of nicotine on tumor tropism to glioma-conditioned medium (CM) at a non-cytotoxic concentration was assessed with Matrigel invasion assay. Nicotine effect on GJIC was assessed with the scrape loading/dye transfer (SL/DT) assay for co-culture of glioma and stem cells and the parachute assay among glioma cells using high-content analysis. Results: Tumor tropism of iPS-NSCs toward GL261-CM and DPSCs toward U251-CM was not affected by nicotine (0.1 and 1 µM). Nicotine at the concentrations equivalent to habitual smoking (1 µM) did not affect GJIC of iPS-NSC/GL261 and DPSC/U251 and GJIC among each glioma cells. Conclusions: The study demonstrated that non-cytotoxic concentrations of nicotine did not significantly change the stem cell properties requisite for stem cell-based suicide gene therapy.

中文翻译：

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尼古丁不会影响针对神经胶质瘤的自杀基因疗法所必需的干细胞特性。

客观的： 

胶质母细胞瘤是成人中枢神经系统中最致命的肿瘤之一，中位生存期为一年半，迫切需要有效的治疗策略。出于这个原因，基于干细胞的自杀基因疗法由于干细胞强大的肿瘤趋向性和旁观者效应而引起了极大的兴趣。在目前的临床情况下，干细胞是用于神经胶质瘤治疗的有前途的自杀基因传递工具。由于习惯性吸烟在世界范围内仍然盛行，我们研究了尼古丁对干细胞对胶质瘤的趋向性以及胶质瘤和干细胞之间的间隙连接细胞间通讯 (GJIC) 功能的影响，这两者对于自杀基因治疗都很重要。方法： 使用小鼠诱导的多能干细胞衍生的神经干细胞 (iPS-NSCs) 和人牙髓间充质干细胞 (DPSCs)。使用 Matrigel 侵袭试验评估尼古丁对非细胞毒性浓度的胶质瘤条件培养基 (CM) 的肿瘤趋向性的影响。尼古丁对 GJIC 的影响通过胶质瘤和干细胞共培养的刮板装载/染料转移 (SL/DT) 测定以及使用高内涵分析的胶质瘤细胞之间的降落伞测定来评估。结果：  iPS-NSCs 对 GL261-CM 和 DPSCs 对 U251-CM 的肿瘤趋向性不受尼古丁（0.1 和 1 µM）的影响。相当于习惯性吸烟 (1 µM) 浓度的尼古丁不影响每个神经胶质瘤细胞中 iPS-NSC/GL261 和 DPSC/U251 和 GJIC 的 GJIC。结论： 该研究表明，非细胞毒性浓度的尼古丁并没有显着改变干细胞自杀基因治疗所需的干细胞特性。