Abstract
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.
Highlights
Based on the fact that dermal papilla cells (DPCs) interaction with epithelial stem cells can induce generation of new hair follicles [1,2,3], the cell therapy using DPCs has emerged as a potentially new approach for hair transplantation [4, 5]
Consistent with the Hoechst/propidium iodide (PI) apoptosis assay, our results indicated that the treatment drug at such concentrations caused neither apoptosis nor necrosis detected by Hoechst and PI, respectively (Figure 1(b))
Advancement in research facilitates the culture of these specialized cells, previous study has shown that the hair inducing property of DPCs is gradually declined during culture [4, 6, 7]
Summary
Based on the fact that dermal papilla cells (DPCs) interaction with epithelial stem cells can induce generation of new hair follicles [1,2,3], the cell therapy using DPCs has emerged as a potentially new approach for hair transplantation [4, 5]. DPCs, the major cell population existing in the mesenchymal compartments, are located at the base of the hair follicle and function as a signaling center in the hair follicle morphogenesis and growth cycle [9]. These cells instruct the epithelial stem cells through specific signals to proliferate and differentiate into multiple layers of the growing hair shaft [1,2,3]. An ablation of stem cell-related transcription factors including Sox in DPCs leads to the impairment of the hair shaft
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