The immunomodulatory and neuroprotective effects of mesenchymal stem cells (MSCs) in experimental autoimmune encephalomyelitis (EAE): a model of multiple sclerosis (MS)

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells that differentiate into the mesenchymal lineages of adipocytes, osteocytes and chondrocytes. MSCs can also transdifferentiate and thereby cross lineage barriers, differentiating for example into neurons under certain experimental conditions. MSCs have anti-proliferative, anti-inflammatory and anti-apoptotic effects on neurons. Therefore, MSCs were tested in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), for their effectiveness in modulating the pathogenic process in EAE to develop effective therapies for MS. The data in the literature have shown that MSCs can inhibit the functions of autoreactive T cells in EAE and that this immunomodulation can be neuroprotective. In addition, MSCs can rescue neural cells via a mechanism that is mediated by soluble factors, which provide a suitable environment for neuron regeneration, remyelination and cerebral blood flow improvement. In this review, we discuss the effectiveness of MSCs in modulating the immunopathogenic process and in providing neuroprotection in EAE.

Keywords: central nervous system (CNS); experimental autoimmune encephalomyelitis (EAE); mesenchymal stem cells (MSC); microglia; neurons; neuroprotection; oligodendrocytes.

Figure 1

The differentiation of naïve T cells into different subtypes of T cells under the influence of cytokines. Interferon-γ (IFN-γ) and IL-12 convert naïve T cells into T helper 1 cells, whereas IL-4 promotes the development of T helper 2 cells. The differentiation of Th17 cells is promoted by IL-1, IL-6 and IL-23, and the differentiation of regulatory T cells requires TGF-β.

Figure 2

Immunomodulatory effects of MSCs on immune cells, including T cells, NK cells, B cells, monocytes and dendritic cells (DCs). MSCs can inhibit the proliferation and the cytotoxic functions of T and NK cells. MSCs can also modulate the functions of B cells. In addition, the differentiation of monocytes into immature DCs is inhibited by MSCs. Moreover, the maturation of DCs and their ability to activate T cells are also affected by MSCs.

Figure 3

Mesenchymal stem cells can induce neuron recovery in multiple sclerosis via a mechanism that stimulates oligodendrogenesis and decreases the numbers of Th1 and Th17 cells and their secretion of inflammatory cytokines while increasing the numbers of Th2 and Treg cells and their secretion of anti-inflammatory cytokines.