title: Functional differences in mesenchymal stromal cells from human dental pulp and periodontal ligament.
abstract: Clinically reported reparative benefits of mesenchymal stromal cells (MSCs) are majorly attributed to strong immune-modulatory abilities not exactly shared by fibroblasts. However, MSCs remain heterogeneous populations, with unique tissue-specific subsets, and lack of clear-cut assays defining therapeutic stromal subsets adds further ambiguity to the field. In this context, in-depth evaluation of cellular characteristics of MSCs from proximal oro-facial tissues: dental pulp (DPSCs) and periodontal ligament (PDLSCs) from identical donors provides an opportunity to evaluate exclusive niche-specific influences on multipotency and immune-modulation. Exhaustive cell surface profiling of DPSCs and PDLSCs indicated key differences in expression of mesenchymal (CD105) and pluripotent/multipotent stem cell-associated cell surface antigens: SSEA4, CD117, CD123 and CD29. DPSCs and PDLSCs exhibited strong chondrogenic potential, but only DPSCs exhibited adipogenic and osteogenic propensities. PDLSCs expressed immuno-stimulatory/immune-adhesive ligands like HLA-DR and CD50, upon priming with IFNγ, unlike DPSCs, indicating differential response patterns to pro-inflammatory cytokines. Both DPSCs and PDLSCs were hypo-immunogenic and did not elicit robust allogeneic responses despite exposure to IFNγ or TNFα. Interestingly, only DPSCs attenuated mitogen-induced lympho-proliferative responses and priming with either IFNγ or TNFα enhanced immuno-modulation capacity. In contrast, primed or unprimed PDLSCs lacked the ability to suppress polyclonal T cell blast responses. This study indicates that stromal cells from even topographically related tissues do not necessarily share identical MSC properties and emphasizes the need for a thorough functional testing of MSCs from diverse sources with respect to multipotency, immune parameters and response to pro-inflammatory cytokines before translational usage.
authors.affiliation: School of Regenerative Medicine (SORM), Manipal University, Bangalore, India.
authors.forename: Anoop Babu
authors.initials: AB
authors.lastname: Vasandan
authors.forename: Shilpa Rani
authors.initials: SR
authors.lastname: Shankar
authors.forename: Priya
authors.initials: P
authors.lastname: Prasad
authors.forename: Vulugundam
authors.initials: V
authors.lastname: Sowmya Jahnavi
authors.forename: Ramesh Ramachandra
authors.initials: RR
authors.lastname: Bhonde
authors.forename: Susarla
authors.initials: S
authors.lastname: Jyothi Prasanna
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D055746:Stage-Specific Embryonic Antigens / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D006684:HLA-DR Antigens; D055746:Stage-Specific Embryonic Antigens; D014409:Tumor Necrosis Factor-alpha; C066584:stage-specific embryonic antigen-4; D007371:Interferon-gamma
keywords: dental pulp stromal cells; differentiation; immune properties; mesenchymal stromal cells; periodontal ligament stromal cells; pro-inflammatory cytokines; stem cells