Jade Griffin

Background: Multiple sclerosis (MS) is a chronic autoimmune disease causing inflammation, demyelination, and neurodegeneration in the central nervous system¹. It is a major cause of disability and is more prevalent in females¹. Risk factors include vitamin D deficiency, smoking, and genetics (HLA-DRB1*15:01)². Immune cells like Th1, Th17, and CD8+ T cells contribute to inflammation². MS typically manifests in young adults with optic neuritis and sensory disturbances, presenting as relapsing-remitting, primary progressive, or secondary progressive forms³. Accepted treatments are disease-modifying therapies (DMTs) for long-term care and corticosteroids for relapses⁴. Current DMTs target autoimmunity to slow progression but cannot reverse neural damage. Stem cell transplantation shows promise for reconstituting tissue, offering hope for managing MS-related disability.

Objective: In this narrative review, we consider the mechanisms of MS inflammation and disease progression and evaluate stem cell transplantation as a potential therapeutic.

Search Methods: An online search in the PubMed database was conducted from 2018 to 2024 using the following keywords: “multiple sclerosis”, “stem cell transplantation”, “immune modulation”, “neuroprotection”, “experimental autoimmune encephalitis”

Results: Studies indicate multiple sclerosis (MS) lesions demonstrate an aggregation of specific immune cells that may be modulated by different treatments. Autopsy analysis of 35 MS cases revealed CD8+ T cells and CD20+ B cells as predominant in lesions, with CD20+ B cells highly characteristic and elevated only in MS samples compared to controls⁵. In MS mouse models of MS experimental autoimmune encephalomyelitis (EAE), treatment with the natural compound DDC blocked Th17 cells and promoted Treg cells, effectively reducing disease severity, inflammation, and demyelination⁶. Injection of bone marrow mesenchymal stem cells (BM-MSCs) into mice with EAE reduced proliferation and activation of CD4+ and CD8+ T cells, increased Treg proliferation, and reduced proinflammatory cytokines⁷. BM-MSC treatment also demonstrated clinical benefits by significantly reducing EAE progression⁷. In a human MS trial, intrathecal injection of human fetal neural precursor stem cells (hfNPCs) was safe, tolerable and feasible⁸. Patients receiving the highest hfNPC dose showed lower brain atrophy rates and increased anti-inflammatory and neuroprotective factors in cerebrospinal fluid⁸. Comparing mesenchymal stem cells (MSCs) versus neural stem cells (NSCs) transplanted into EAE mice, NSCs had a greater therapeutic effect, increasing Tregs and decreasing Th17 cells to a greater extent than MSCs⁹. NSC treatment also provided greater disease amelioration, with treated mice developing near-normal clinical scores and significantly reduced inflammation⁹.

Conclusion: The use of stem cell transplantation in multiple sclerosis models has shown promise as a potential therapy. Studies have identified the primary immune phenotypes involved in MS with CD20+ B cells characterizing lesions, and CD8+ T cells being related to inflammation⁵. Stem cell transplantation has been shown to reconstitute the immune cell differentiation pathway in MS models and reduce disease inflammation and demyelination. Questions for further research should be directed at refining the mechanism of immune response in MS as compared to the MS mouse model, EAE as well as continuing to assess stem cell therapy application to human MS patients.

Works Cited:

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8. Genchi A, Brambilla E, Sangalli F, et al. Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study. Nat Med. 2023;29(1):75-85. doi:10.1038/s41591-022-02097-3
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