title: Periodontal Tissue Regeneration Using Syngeneic Adipose-Derived Stromal Cells in a Mouse Model.
abstract: Current treatment of periodontitis is still associated with a high degree of variability in clinical outcomes. Recent advances in regenerative medicine by mesenchymal cells, including adipose stromal cells (ASC) have paved the way to improved periodontal regeneration (PD) but little is known about the biological processes involved. Here, we aimed to use syngeneic ASCs for periodontal regeneration in a new, relevant, bacteria-induced periodontitis model in mice. Periodontal defects were induced in female C57BL6/J mice by oral gavage with periodontal pathogens. We grafted 2 × 105syngeneic mouse ASCs expressing green fluorescent protein (GFP) (GFP+/ASC) within a collagen vehicle in the lingual part of the first lower molar periodontium (experimental) while carrier alone was implanted in the contralateral side (control). Animals were sacrificed 0, 1, 6, and 12 weeks after treatment by GFP+/ASC or vehicle graft, and microscopic examination, immunofluorescence, and innovative bio-informatics histomorphometry methods were used to reveal deep periodontium changes. From 1 to 6 weeks after surgery, GFP+ cells were identified in the periodontal ligament (PDL), in experimental sites only. After 12 weeks, cementum regeneration, the organization of PDL fibers, the number of PD vessels, and bone morphogenetic protein-2 and osteopontin expression were greater in experimental sites than in controls. Specific stromal cell subsets were recruited in the newly formed tissue in ASC-implanted periodontium only. These data suggest that ASC grafting in diseased deep periodontium, relevant to human pathology, induces a significant improvement of the PDL microenvironment, leading to a recovery of tooth-supporting tissue homeostasis. Stem Cells Translational Medicine 2017;6:656-665.
authors.affiliation: Department of Biological Sciences, Dental Faculty, Toulouse University Hospital, University of Toulouse, Toulouse, France.|CNRS ERL 5311, EFS, INPENVT, INSERM U1031, UPS, STROMALab, University of Toulouse, Toulouse, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemaitre
authors.affiliation: CNRS ERL 5311, EFS, INPENVT, INSERM U1031, UPS, STROMALab, University of Toulouse, Toulouse, France.|Department of Anatomical Sciences and Radiology, Dental Faculty, Toulouse University Hospital, University of Toulouse, Toulouse, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Monsarrat
authors.affiliation: Department of Biological Sciences, Dental Faculty, Toulouse University Hospital, University of Toulouse, Toulouse, France.|UMR1048, I2MC, UPS, INSERM, University of Toulouse, Toulouse, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Blasco-Baque
authors.affiliation: Department of Biological Sciences, Dental Faculty, Toulouse University Hospital, University of Toulouse, Toulouse, France.|UMR1048, I2MC, UPS, INSERM, University of Toulouse, Toulouse, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Loubières
authors.affiliation: UMR1048, I2MC, UPS, INSERM, University of Toulouse, Toulouse, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Burcelin
authors.affiliation: CNRS ERL 5311, EFS, INPENVT, INSERM U1031, UPS, STROMALab, University of Toulouse, Toulouse, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
authors.affiliation: CNRS ERL 5311, EFS, INPENVT, INSERM U1031, UPS, STROMALab, University of Toulouse, Toulouse, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Planat-Bénard
authors.affiliation: Department of Biological Sciences, Dental Faculty, Toulouse University Hospital, University of Toulouse, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Kémoun
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D051929:CD146 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D016967:Fusobacterium nucleatum / Q000472:pathogenicity; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053495:Osteopontin / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology / Q000601:surgery*; D010519:Periodontium / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology / Q000601:surgery*; D010641:Phenotype; D016966:Porphyromonas gingivalis / Q000472:pathogenicity; D018713:Prevotella intermedia / Q000472:pathogenicity; D012038:Regeneration; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000637:transplantation*; D013997:Time Factors; D014185:Transplantation, Isogeneic
chemical_list: D000950:Antigens, Ly; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D051929:CD146 Antigen; C074650:Ly6a protein, mouse; C497903:Mcam protein, mouse; D008565:Membrane Proteins; C506896:Spp1 protein, mouse; D053495:Osteopontin
keywords: Mesenchymal stem cell transplantation; Mesenchymal stromal cells; Mice; Periodontitis; Regenerative medicine; Subcutaneous fat