title: Periodontal-ligament-derived stem cells exhibit the capacity for long-term survival, self-renewal, and regeneration of multiple tissue types in vivo.
abstract: Primary periodontal ligament stem cells (PDLSCs) are known to possess multidifferentiation potential and exhibit an immunophenotype similar to that described for bone-marrow-derived mesenchymal stem cells. In the present study, bromo-deoxyuridine (BrdU)-labeled ovine PDLSCs implanted into immunodeficient mice survived after 8 weeks post-transplantation and exhibited the capacity to form bone/cementum-like mineralized tissue, ligament structures similar to Sharpey's fibers with an associated vasculature. To evaluate self-renewal potential, PDLSCs were recovered from harvested primary transplants 8 weeks post-transplantation that exhibit an immunophenotype and multipotential capacity comparable to primary PDLSCs. The re-derived PDLSCs isolated from primary transplants were implanted into secondary ectopic xenogeneic transplants. Histomorphological analysis demonstrated that four out of six donor re-derived PDLSC populations displayed a capacity to survive and form fibrous ligament structures and mineralized tissues associated with vasculature in vivo, although at diminished levels in comparison to primary PDLSCs. Further, the capacity for long-term survival and the potential role of PDLSCs in dental tissue regeneration were determined using an ovine preclinical periodontal defect model. Autologous ex vivo-expanded PDLSCs that were prelabeled with BrdU were seeded onto Gelfoam(®) scaffolds and then transplanted into fenestration defects surgically created in the periodontium of the second premolars. Histological assessment at 8 weeks post-implantation revealed surviving BrdU-positive PDLSCs associated with regenerated periodontium-related tissues, including cementum and bone-like structures. This is the first report to demonstrate the self-renewal capacity of PDLSCs using serial xenogeneic transplants and provides evidence of the long-term survival and tissue contribution of autologous PDLSCs in a preclinical periodontal defect model.
authors.affiliation: 1 Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide , Adelaide, Australia .
authors.forename: Danijela
authors.initials: D
authors.lastname: Menicanin
authors.forename: Krzysztof Marek
authors.initials: KM
authors.lastname: Mrozik
authors.forename: Naohisa
authors.initials: N
authors.lastname: Wada
authors.forename: Victor
authors.initials: V
authors.lastname: Marino
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
authors.forename: P Mark
authors.initials: PM
authors.lastname: Bartold
authors.forename: Stan
authors.initials: S
authors.lastname: Gronthos
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D064593:Heterografts; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D012756:Sheep; D033581:Stem Cell Transplantation; D013997:Time Factors