Mechanism of Multiple Sclerosis Stem Cell Therapy

Friday July 24th, 2009 @ 13:04:52 EST

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Cleveland, Ohio -

A recent study (Bai et al. Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia. 2009 Aug 15;57(11):1192-203) asked the question of whether human mesenchymal stem cells may be useful in the treatment of the mouse model of multiple sclerosis, experimental allergic encephalomyelitis (EAE).

Mesenchymal stem cells are known to stimulate various shifts in immune response, due to a variety of soluble and membrane bound factors. For example, mesenchymal stem cells produce LIF, HLA-G, and stimulate generation of T regulatory cells, which are believed to be beneficial in multiple sclerosis.

Patients treated with adipose derived mononuclear cells (stromal vascular fraction), which is comprised of several cell types, including mesenchymal stem cells, have shown improvement.

In the current paper, the authors addressed the question of whether mesenchymal stem cells are capable of inhibiting multiple sclerosis in the classical EAE model. Most interestingly, the authors were curious whether human mesenchymal stem cells would work. This is a very interesting question since one would expect any human cell placed into an immune competent mouse to be rejected.

The authors used two types of EAE models. The first, is a chronic-progressive, which involved immunization of B6 mice with myelin oligodendrocyte protein (MOG)-derived peptides. The second model is a relapse-remitting model, which was induced by immunizing SJL mice with proteolipid protein peptide (PLP). A disease severity score was used in which 0 indicates no disease and 5 means death.

When B6 mice were treated with mesenchymal stem cells on day 16 or 26 after immunization disease remission was noticed. Remission was also noted in the relapse-remitting model.

Reduction of lymphocyte infiltration was noted in the CNS as detected by reduction in CD45 positive cell staining. Additionally, mesenchymal stem cell therapy was associated with improved myelination, smaller lesion area, and increased restoration of axons.

Mechanistically it seemed that administered MSC entered the CNS and seemed to induce increased numbers of oligodendrocytes. Immune deviation was seen in recall response by reduced IFN-g, IL-2, and IL-17, suppression of TNF and IL-12, and increased IL-4 and IL-5.

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