Kiratipaiboon Chayanin, Tengamnuay Parkpoom, Chanvorachote Pithi
Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Stem Cells Int. 2016;2016:5831276. doi: 10.1155/2016/5831276. Epub 2015 Nov 16.
Improvement in the expansion method of adult stem cells may augment their use in regenerative therapy. Using human dermal papilla cell line as well as primary dermal papilla cells as model systems, the present study demonstrated that ciprofloxacin treatment could prevent the loss of stemness during culture. Clonogenicity and stem cell markers of dermal papilla cells were shown to gradually decrease in the culture in a time-dependent manner. Treatment of the cells with nontoxic concentrations of ciprofloxacin could maintain both stem cell morphology and clonogenicity, as well as all stem cells markers. We found that ciprofloxacin exerted its effect through ATP-dependent tyrosine kinase/glycogen synthase kinase3β dependent mechanism which in turn upregulated β-catenin. Besides, ciprofloxacin was shown to induce epithelial-mesenchymal transition in DPCs as the transcription factors ZEB1 and Snail were significantly increased. Furthermore, the self-renewal proteins of Wnt/β-catenin pathway, namely, Nanog and Oct-4 were significantly upregulated in the ciprofloxacin-treated cells. The effects of ciprofloxacin in preserving stem cell features were confirmed in the primary dermal papilla cells directly obtained from human hair follicles. Together, these results revealed a novel application of ciprofloxacin for stem cell maintenance and provided the underlying mechanisms that are responsible for the stemness in dermal papilla cells.
成人干细胞扩增方法的改进可能会增加其在再生治疗中的应用。本研究以人真皮乳头细胞系以及原代真皮乳头细胞作为模型系统,证明环丙沙星处理可防止培养过程中干细胞特性的丧失。真皮乳头细胞的克隆形成能力和干细胞标志物在培养过程中呈时间依赖性逐渐下降。用无毒浓度的环丙沙星处理细胞可维持干细胞形态、克隆形成能力以及所有干细胞标志物。我们发现环丙沙星通过ATP依赖性酪氨酸激酶/糖原合酶激酶3β依赖性机制发挥作用,进而上调β-连环蛋白。此外,环丙沙星可诱导真皮乳头细胞发生上皮-间质转化,因为转录因子ZEB1和Snail显著增加。此外,在经环丙沙星处理的细胞中,Wnt/β-连环蛋白通路的自我更新蛋白,即Nanog和Oct-4显著上调。在直接从人毛囊获得的原代真皮乳头细胞中证实了环丙沙星在保留干细胞特性方面的作用。总之,这些结果揭示了环丙沙星在干细胞维持方面的新应用,并提供了真皮乳头细胞中干细胞特性的潜在机制。