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Stem cells from human apical papilla decrease neuro-inflammation and stimulate oligodendrocyte progenitor differentiation via activin-A secretion
Authors:Pauline De Berdt  Pauline Bottemanne  John Bianco  Mireille Alhouayek  Anibal Diogenes  Amy Llyod  Jose Gerardo-Nava  Gary A Brook  Véronique Miron  Giulio G Muccioli  Anne des Rieux
Institution:1.Louvain Drug Research Institute (LDRI), Advanced Drug Delivery and Biomaterials (ADDB),Université Catholique de Louvain,Brussels,Belgium;2.Louvain Drug Research Institute, Bioanalysis and Pharmacology of Bioactive Lipids Research Group (BPBL),Université Catholique de Louvain,Brussels,Belgium;3.Department of Endodontics,University of Texas Health Science Center at San Antonio,Texas,USA;4.MRC Center for Reproductive Health, The Queen’s Medical Research Institute,The University of Edinburgh,Edinburgh,UK;5.Institute of Neuropathology,Uniklinik RWTH Aachen,Aachen,Germany
Abstract:Secondary damage following spinal cord injury leads to non-reversible lesions and hampering of the reparative process. The local production of pro-inflammatory cytokines such as TNF-α can exacerbate these events. Oligodendrocyte death also occurs, followed by progressive demyelination leading to significant tissue degeneration. Dental stem cells from human apical papilla (SCAP) can be easily obtained at the removal of an adult immature tooth. This offers a minimally invasive approach to re-use this tissue as a source of stem cells, as compared to biopsying neural tissue from a patient with a spinal cord injury. We assessed the potential of SCAP to exert neuroprotective effects by investigating two possible modes of action: modulation of neuro-inflammation and oligodendrocyte progenitor cell (OPC) differentiation. SCAP were co-cultured with LPS-activated microglia, LPS-activated rat spinal cord organotypic sections (SCOS), and LPS-activated co-cultures of SCOS and spinal cord adult OPC. We showed for the first time that SCAP can induce a reduction of TNF-α expression and secretion in inflamed spinal cord tissues and can stimulate OPC differentiation via activin-A secretion. This work underlines the potential therapeutic benefits of SCAP for spinal cord injury repair.
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