Characterisation of human dental pulp stem cells in an animal model of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) in which autoimmune inflammation destroys the protective myelin sheath that insulates axons. This leads to many symptoms including paralysis, it causes severe morbidity and is one of the most common neurological diseases affecting young adults. New treatments are urgently required for MS patients as none of the currently available disease-modifying therapies support repair of the damaged CNS. Ideally, future treatments for MS would encompass both suppression of autoimmunity and facilitate repair of the damaged CNS. Mesenchymal stem cells (MSCs) have the potential to fill both these criteria and therefore represent an attractive therapy for MS. Human dental pulp stem cells (DPSCs) are a type of MSC originating from neural crest cells and therefore more closely related to neuronal cell types than MSCs from other anatomical sources. Thus, DPSCs are potentially a more suitable therapeutic candidate than other MSCs for treatment of CNS disorders including MS. In this study the suitability of DPSCs as a therapeutic for MS was tested in a mouse model, experimental autoimmune encephalomyelitis (EAE). DPSCs were isolated from the third molars of different donors and characterised in vitro. All DPSCs obtained adhered to MSC classification criteria and could be maintained continuously in culture for several weeks. Effects of DPSCs on the clinical course of EAE was thoroughly tested. Donor-to-donor variability was apparent with regard to the suppressive effect of these treatments on clinical EAE. Some donor’s DPSCs were potently inhibitory to clinical EAE while DPSCs from other donors showed no significant suppression of disease. No evidence was found to support DPSC recruitment to the CNS or long-term engraftment. DPSCs that inhibited EAE impaired generation of Th17 cell responses and increased the ratio of Th1:Th17 cells in the spleen and CNS. DPSC treatment of EAE mice also resulted in significantly fewer lymphocytes, infiltrating myeloid cells and fewer microglia in the CNS. Secreted factors from DPSCs were implicated in this as conditioned medium from DPSCs was able to suppress differentiation of Th17 cells in vitro. DPSCs also suppressed the activation of B cells and their differentiation to antibody-secreting plasmablasts in vitro. Collectively, the data in this study reveals some potential for DPSCs to be therapeutic for neuroinflammatory disorders, although the donor-to-donor variability in these effects warrants further investigation. Key cells of the immune system involved in MS pathogenesis have been identified to be modulated by DPSC treatment in EAE, although further investigation is required to elucidate the molecular mechanisms by which DPSCs suppress those cell subsets in EAE.