naa a22 4500 510739474 CHVBK 20180411083023.0 cr unu---uuuuu 180411e20131001xx s 000 0 eng 10.1007/s12015-013-9442-7 doi (NATIONALLICENCE)springer-10.1007/s12015-013-9442-7 SCF Promotes Dental Pulp Progenitor Migration, Neovascularization, and Collagen Remodeling - Potential Applications as a Homing Factor in Dental Pulp Regeneration [Elektronische Daten] [Shuang Pan, Smit Dangaria, Gokul Gopinathan, Xiulin Yan, Xuanyu Lu, Antonia Kolokythas, Yumei Niu, Xianghong Luan] Stem cell factor (SCF) is a powerful chemokine that binds to the c-Kit receptor CD117 and has shown promise as a homing agent capable of progenitor cell recruitment. In the present study we have documented high levels of both SCF and its receptor c-Kit in differentiating dental pulp (DP) cells and in the sub-odontoblastic layer of Höhl. In vitro studies using human DP progenitors revealed a significant increase in cell proliferation after100nM SCF application, explained by a 2-fold upregulation in cyclin D3 and FGF2 cell cycle regulators, and a 7-fold increase in CDK4 expression. DP cell migration in the presence of SCF was up-regulated 2.7-fold after a 24h culture period, and this effect was accompanied by cytoskeletal rearrangement, a 1.5-fold increase in polymeric F-actin over G-actin, and a 1.8-fold increase in RhoA expression. Explaining the signaling effect of SCF on DP migration, PI3K/Akt and MEK/ERK pathway inhibitors were demonstrated to significantly reduce DP cell migration, while SCF alone doubled the number of migrated cells. ERK and AKT phosphorylation were dramatically upregulated already 3-5min after SCF addition to the culture medium and declined thereafter, classifying SCF as a fast acting chemokine. When applied as an agent to promote tissue regeneration in subcutaneously implanted collagen sponges, SCF resulted in a 7-fold increase in the cell number in the implanted tissue construct, a more than 9-fold increase in capillaries, as well as collagen sponge remodeling and collagen fiber neogenesis. Together, these studies demonstrate the suitability of SCF as a potent aid in the regeneration of dental pulp and other mesenchymal tissues, capable of inducing cell homing, angiogenesis, and tissue remodeling. Springer Science+Business Media New York, 2013 Dental pulp nationallicence SCF nationallicence Homing nationallicence Stem cells nationallicence Regeneration nationallicence Pan Shuang School of Dentistry, Department of Endodontics, Harbin Medical University, Harbin, China aut Dangaria Smit Department of Oral Biology, UIC College of Dentistry, Chicago, IL, USA aut Gopinathan Gokul Department of Oral Biology, UIC College of Dentistry, Chicago, IL, USA aut Yan Xiulin Department of Oral Biology, UIC College of Dentistry, Chicago, IL, USA aut Lu Xuanyu Department of Oral Biology, UIC College of Dentistry, Chicago, IL, USA aut Kolokythas Antonia Department of Oral Surgery, UIC College of Dentistry, Chicago, IL, USA aut Niu Yumei School of Dentistry, Department of Endodontics, Harbin Medical University, Harbin, China aut Luan Xianghong Department of Oral Biology, UIC College of Dentistry, Chicago, IL, USA aut Stem Cell Reviews and Reports Springer US; http://www.springer-ny.com 9/5(2013-10-01), 655-667 1550-8943 9:5<655 2013 9 12015 https://doi.org/10.1007/s12015-013-9442-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12015-013-9442-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pan Shuang School of Dentistry, Department of Endodontics, Harbin Medical University, Harbin, China aut NATIONALLICENCE 700 1- Dangaria Smit Department of Oral Biology, UIC College of Dentistry, Chicago, IL, USA aut NATIONALLICENCE 700 1- Gopinathan Gokul Department of Oral Biology, UIC College of Dentistry, Chicago, IL, USA aut NATIONALLICENCE 700 1- Yan Xiulin Department of Oral Biology, UIC College of Dentistry, Chicago, IL, USA aut NATIONALLICENCE 700 1- Lu Xuanyu Department of Oral Biology, UIC College of Dentistry, Chicago, IL, USA aut NATIONALLICENCE 700 1- Kolokythas Antonia Department of Oral Surgery, UIC College of Dentistry, Chicago, IL, USA aut NATIONALLICENCE 700 1- Niu Yumei School of Dentistry, Department of Endodontics, Harbin Medical University, Harbin, China aut NATIONALLICENCE 700 1- Luan Xianghong Department of Oral Biology, UIC College of Dentistry, Chicago, IL, USA aut NATIONALLICENCE 773 0- Stem Cell Reviews and Reports Springer US; http://www.springer-ny.com 9/5(2013-10-01), 655-667 1550-8943 9:5<655 2013 9 12015 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer