title: Conditioned medium of periodontal ligament mesenchymal stem cells exert anti-inflammatory effects in lipopolysaccharide-activated mouse motoneurons.
abstract: Conditioned medium derived from mesenchymal stem cells (MSCs) shows immunomodulatory and neuroprotective effects in preclinical models. Given the difficulty to harvest MSCs from bone marrow and adipose tissues, research has been focused to find alternative resources for MSCs, such as oral-derived tissues. Recently, we have demonstrated the protective effects of MSCs obtained from healthy human periodontal ligament tissue (hPDLSCs) in murine experimental autoimmune encephalomyelitis model. In the present in vitro study, we have investigated the immunomodulatory and neuroprotective effects of conditioned medium obtained from hPDLSCs of Relapsing Remitting- Multiple sclerosis (RR-MS) patients on NSC34 mouse motoneurons stimulated with lipopolysaccharide (LPS). Immunocytochemistry and western blotting were performed. Increased level of TLR4 and NFκB, and reduced level of IκB-α were observed in LPS-stimulated motoneurons, which were modulated by pre-conditioning with hPDLSC-conditioned medium. Inflammatory cytokines (TNF-α, IL-10), neuroprotective markers (Nestin, NFL 70, NGF, GAP43), and apoptotic markers (Bax, Bcl-2, p21) were modulated. Moreover, extracellular vesicles of hPDLSC-conditioned medium showed the presence of anti-inflammatory cytokines IL-10 and TGF-β. Our results demonstrate the immunosuppressive properties of hPDLSC-conditioned medium of RR-MS patients in motoneurons subjected to inflammation. Our findings warrant further preclinical and clinical studies to elucidate the autologous therapeutic efficacy of hPDLSC-conditioned medium in neurodegenerative diseases.
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
authors.forename: Thangavelu Soundara
authors.initials: TS
authors.lastname: Rajan
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Giacoppo
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti-Pescara, Chieti, Italy.
authors.forename: Oriana
authors.initials: O
authors.lastname: Trubiani
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti-Pescara, Chieti, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Diomede
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti-Pescara, Chieti, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Piattelli
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy. Electronic address: emazzon.irccs@gmail.com.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology; D010513:Periodontal Ligament / Q000166:cytology*; D000067996:RAW 264.7 Cells; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: Conditioned medium; Human Periodontal ligament mesenchymal stem cells; Lipopolysaccharide; Motoneurons; Neuroinflammation; Neuroprotection