Abstract

BackgroundMultiple sclerosis is a demyelinating disease mostly of autoimmune origin that affects and damages the central nervous system, leading to a disabling condition. The aim of the present study was to investigate whether administration of mesenchymal stem cells from human periodontal ligament (hPDLSCs) could ameliorate multiple sclerosis progression by exerting neuroprotective effects in an experimental model of autoimmune encephalomyelitis (EAE).MethodsEAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35–55 in C57BL/6 mice. After immunization, mice were observed every 48 hours for signs of EAE and weight loss. At the onset of disease, approximately 14 days after immunization, EAE mice were subjected to a single intravenous injection of hPDLSCs (106 cells/150 μl) into the tail vein. At the point of animal sacrifice on day 56 after EAE induction, spinal cord and brain tissues were collected in order to perform histological evaluation, immunohistochemistry and western blotting analysis.ResultsAchieved results reveal that treatment with hPDLSCs may exert neuroprotective effects against EAE, diminishing both clinical signs and histological score typical of the disease (lymphocytic infiltration and demyelination) probably through the production of neurotrophic factors (results focused on brain-derived neurotrophic factor and nerve growth factor expression). Furthermore, administration of hPDLSCs modulates expression of inflammatory key markers (tumor necrosis factor-α, interleukin (IL)-1β, IL-10, glial fibrillary acidic protein, Nrf2 and Foxp3), the release of CD4 and CD8α T cells, and the triggering of apoptotic death pathway (data shown for cleaved caspase 3, p53 and p21).ConclusionsIn light of the achieved results, transplantation of hPDLSCs may represent a putative novel and helpful tool for multiple sclerosis treatment. These cells could have considerable implication for future therapies for multiple sclerosis and this study may represent the starting point for further investigations.

Highlights

  • Multiple sclerosis is a demyelinating disease mostly of autoimmune origin that affects and damages the central nervous system, leading to a disabling condition

  • The potential role of mesenchymal stem cells (MSCs), derived especially from bone marrow, in promoting tissue repair and disease control has been investigated by using an experimental autoimmune encephalomyelitis (EAE) model [4,5,6,7], the most common animal model that mimics the main features of human Multiple sclerosis (MS) [8]

  • This study aimed to investigate the possible neuroprotective effect of human periodontal ligament stem cell (hPDLSC) administration against the overall cascade of events occurring after EAE induction in C57BL/6 mice by improving development and clinical signs of disease

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Summary

Introduction

Multiple sclerosis is a demyelinating disease mostly of autoimmune origin that affects and damages the central nervous system, leading to a disabling condition. The aim of the present study was to investigate whether administration of mesenchymal stem cells from human periodontal ligament (hPDLSCs) could ameliorate multiple sclerosis progression by exerting neuroprotective effects in an experimental model of autoimmune encephalomyelitis (EAE). Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS). The potential role of mesenchymal stem cells (MSCs), derived especially from bone marrow, in promoting tissue repair and disease control has been investigated by using an experimental autoimmune encephalomyelitis (EAE) model [4,5,6,7], the most common animal model that mimics the main features of human MS [8]. It is probable that neuroprotective effects may result from release of anti-apoptotic proteins as well as neurotrophic factors [12, 13]

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