title: Fighting for territories: time-lapse analysis of dental pulp and dental follicle stem cells in co-culture reveals specific migratory capabilities.
abstract: Stem cell migration is a critical step during the repair of damaged tissues. In order to achieve appropriate cell-based therapies for tooth and periodontal ligament repair it is necessary first to understand the dynamics of tissue-specific stem cell populations such as dental pulp stem cells (DPSC) and dental follicle stem cells (DFSC). Using time-lapse imaging, we analysed migratory and proliferative capabilities of these two human stem cell lines in vitro. When cultured alone, both DPSC and DFSC exhibited low and irregular migration profiles. In co-cultures, DFSC, but not DPSC, spectacularly increased their migration activity and velocity. DFSC rapidly surrounded the DPSC, thus resembling the in vivo developmental process, where follicle cells encircle both dental epithelium and pulp. Cell morphology was dependent on the culture conditions (mono-culture or co-culture) and changed over time. Regulatory genes involved in dental cell migration and differentiation such as TWIST1, MSX1, RUNX2, SFRP1 and ADAM28, were also evaluated in co-cultures. MSX1 up-regulation indicates that DPSC and DFSC retain their odontogenic potential. However, DPSC lose their capacity to differentiate into odontoblasts in the presence of DFSC, as suggested by RUNX2 up-regulation and TWIST1 down-regulation. In contrast, the unchanged levels of SFRP1 expression suggest that DFSC retain their potential to form periodontal tissues even in the presence of DPSC. These findings demonstrate that stem cells behave differently according to their environment, retain their genetic memory, and compete with each other to acquire the appropriate territory. Understanding the mechanisms involved in stem cell migration may lead to new therapeutic approaches for tooth repair.
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology, Second University of Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Schiraldi
authors.forename: A
authors.initials: A
authors.lastname: Stellavato
authors.forename: A
authors.initials: A
authors.lastname: D'Agostino
authors.forename: V
authors.initials: V
authors.lastname: Tirino
authors.forename: R
authors.initials: R
authors.lastname: d'Aquino
authors.forename: A
authors.initials: A
authors.lastname: Woloszyk
authors.forename: A
authors.initials: A
authors.lastname: De Rosa
authors.forename: L
authors.initials: L
authors.lastname: Laino
authors.forename: G
authors.initials: G
authors.lastname: Papaccio
authors.forename: T A
authors.initials: TA
authors.lastname: Mitsiadis
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D018920:Coculture Techniques; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D003795:Dental Sac / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014158:Transcription, Genetic; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D051722:ADAM Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D036341:Intercellular Signaling Peptides and Proteins; D051957:MSX1 Transcription Factor; D008565:Membrane Proteins; D009687:Nuclear Proteins; D051879:Twist-Related Protein 1; C484083:MSX1 protein, human; C493709:RUNX2 protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C103173:TWIST1 protein, human; C410224:ADAM28 protein, human