The Beneficial Effect of Human Amnion Mesenchymal Cells in Inhibition of Inflammation and Induction of Neuronal Repair in EAE Mice

Abstract

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Currently, there is still lack of curative treatment for MS. Mesenchymal stem cell- (MSC-) based therapy is recently the subject of intense interest in autoimmune diseases. Here, we investigated the therapeutic effect and potential mechanism of human amnion mesenchymal cells (hAMC) on inflammation and remyelination in experimental autoimmune encephalomyelitis (EAE) mice. C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide. hAMC were injected intraperitoneal when EAE was successfully established. The results demonstrated that application of hAMC significantly ameliorated the disease severity and histopathological changes in EAE mice. The production of proinflammatory cytokines such as IFN-γ, TNF-α, IL-1β, and IL-17A in the spleen and CNS was dramatically inhibited. Moreover, CD4+ T cells and CD8+ T cells in the CNS were also significantly decreased in EAE mice after hAMC treatment. In addition, hAMC treatment also promoted the production of neuron-repair factors (NGF, CNTF, and BDNF) in the CNS of EAE mice. In conclusion, these results indicated that hAMC could attenuate the inflammation and promote the remyelination in EAE mice, which might be a promising cell source for the therapy of MS.

Potential Therapeutic Features of Human Amniotic Mesenchymal Stem Cells in Multiple Sclerosis: Immunomodulation, Inflammation Suppression, Angiogenesis Promotion, Oxidative Stress Inhibition, Neurogenesis Induction, MMPs Regulation, and Remyelination Stimulation

“…Treatment of MS with hAMSCs could significantly increase the expression of neurotrophic factors including NGF, CNTF, and BDNF (51). Neurotrophins prevent neurons from initiating programmed cell death and improve survival, development, and function of neurons (15, 52, 53).…”

Human Amniotic Mesenchymal Stem Cells Promote Endogenous Bone Regeneration

“…Although the pathological characteristics of these joint disorders are different, the joint symptoms are associated with abnormal autoimmune function, inflammatory cell infiltration, and joint structural lesions ( 5 ). Stem cells, including hAMSCs, have been introduced to arthritis models, such as rat, to improve the treatment by inhibiting inflammation, regulating the status of autoimmunity, and promoting tissue regeneration ( Table 1 ) ( 55 , 64 , 65 ).…”

“…The immunomodulatory and anti-inflammatory properties of hAMSCs indicated the therapeutic potential for the treatment of RA. In the classic rat arthritis model for human RA, hAMSCs significantly ameliorated the severity of arthritis and decreased the histopathological changes due to dramatic inhibition of the production of proinflammatory cytokines, such as interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) ( 55 ). For a T cell-mediated disease, such as RA, the therapeutic effects of hAMSCs are crucial because they could remarkably restore the CD4+/CD8+ T-cell ratio and inhibit the response of T-cells ( 55 ).…”

“…In the classic rat arthritis model for human RA, hAMSCs significantly ameliorated the severity of arthritis and decreased the histopathological changes due to dramatic inhibition of the production of proinflammatory cytokines, such as interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) ( 55 ). For a T cell-mediated disease, such as RA, the therapeutic effects of hAMSCs are crucial because they could remarkably restore the CD4+/CD8+ T-cell ratio and inhibit the response of T-cells ( 55 ). In addition, hAMSCs suppressed the antigen-specific Th1/Th17 activation and stimulated the generation of CD4+CD25+FoxP3+ Treg cells ( 56 ).…”

Macrophages inhibit adipogenic differentiation of adipose tissue derived mesenchymal stem/stromal cells by producing pro-inflammatory cytokines

“…IFN-γ in combination with any one of TNF-α/IL-1α/IL-1β can endow MSCs with immunomodulatory capability, mainly in an indoleamine 2, 3-dioxidase (IDO)/inducible nitric oxide synthase (iNOS)-dependent manner hinging on species difference [10,11]. Accordingly, MSCs-based cell therapy can modulate immune microenvironment and dampen immune and inflammatory responses associated with graft-versus-host-disease (GVHD) [12], systemic lupus erythematosus (SLE) [13] and experimental autoimmune encephalomyelitis (EAE) [14].…”