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Ciprofloxacin Improves the Stemness of Human Dermal Papilla Cells.

Kiratipaiboon C, Tengamnuay P, Chanvorachote P - Stem Cells Int (2015)

Bottom Line: We found that ciprofloxacin exerted its effect through ATP-dependent tyrosine kinase/glycogen synthase kinase3β dependent mechanism which in turn upregulated β-catenin.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.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

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.

No MeSH data available.


Schematic diagram summarizes the effects of CIP for improvement of the stemness in human DPCs. CIP improved the stemness of human DPCs through Akt activation which accounts for GSK3β inactivation, resulting in the increase of cellular β-catenin. As a consequence, β-catenin accumulates in cytoplasm and translocates into nucleus leading to stimulation of target genes, including transcription factors associated with EMT and self-renewal that might exert the stemness sustaining effect of CIP.
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fig6: Schematic diagram summarizes the effects of CIP for improvement of the stemness in human DPCs. CIP improved the stemness of human DPCs through Akt activation which accounts for GSK3β inactivation, resulting in the increase of cellular β-catenin. As a consequence, β-catenin accumulates in cytoplasm and translocates into nucleus leading to stimulation of target genes, including transcription factors associated with EMT and self-renewal that might exert the stemness sustaining effect of CIP.

Mentions: In closing, we systemically evaluated the positive role of CIP treatment for the maintenance of stemness in cultured DPCs. We identified a novel finding on the stemness regulatory effect of CIP in DPCs, that is, through Akt/GSK3β-dependent β-catenin signal resulting in an upregulation of transcription factors associated with EMT and self-renewal (Figure 6). This information may open the door to further investigations and make this new application of the drug in culture be useful for the cell therapeutic approaches.


Ciprofloxacin Improves the Stemness of Human Dermal Papilla Cells.

Kiratipaiboon C, Tengamnuay P, Chanvorachote P - Stem Cells Int (2015)

Schematic diagram summarizes the effects of CIP for improvement of the stemness in human DPCs. CIP improved the stemness of human DPCs through Akt activation which accounts for GSK3β inactivation, resulting in the increase of cellular β-catenin. As a consequence, β-catenin accumulates in cytoplasm and translocates into nucleus leading to stimulation of target genes, including transcription factors associated with EMT and self-renewal that might exert the stemness sustaining effect of CIP.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663358&req=5

fig6: Schematic diagram summarizes the effects of CIP for improvement of the stemness in human DPCs. CIP improved the stemness of human DPCs through Akt activation which accounts for GSK3β inactivation, resulting in the increase of cellular β-catenin. As a consequence, β-catenin accumulates in cytoplasm and translocates into nucleus leading to stimulation of target genes, including transcription factors associated with EMT and self-renewal that might exert the stemness sustaining effect of CIP.
Mentions: In closing, we systemically evaluated the positive role of CIP treatment for the maintenance of stemness in cultured DPCs. We identified a novel finding on the stemness regulatory effect of CIP in DPCs, that is, through Akt/GSK3β-dependent β-catenin signal resulting in an upregulation of transcription factors associated with EMT and self-renewal (Figure 6). This information may open the door to further investigations and make this new application of the drug in culture be useful for the cell therapeutic approaches.

Bottom Line: We found that ciprofloxacin exerted its effect through ATP-dependent tyrosine kinase/glycogen synthase kinase3β dependent mechanism which in turn upregulated β-catenin.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.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

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.

No MeSH data available.