Mesenchymal stem cell therapy: A review of clinical trials for multiple sclerosis

Asma Alanazi; Mohammad Alassiri; Dunia Jawdat; Yaser Almalik

doi:10.1016/j.reth.2022.07.003

Mesenchymal stem cell therapy: A review of clinical trials for multiple sclerosis

Regen Ther. 2022 Aug 23:21:201-209. doi: 10.1016/j.reth.2022.07.003. eCollection 2022 Dec.

Authors

Asma Alanazi^{1

2}, Mohammad Alassiri^{3

2}, Dunia Jawdat^{3

2}, Yaser Almalik^{1

2

4}

Affiliations

¹ College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
² King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
³ College of Science and Health Professions, Riyadh, Saudi Arabia.
⁴ Division of Neurology, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia.

Abstract

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is the result of the body's own immune cells being auto-reactive to the myelin regions of the body as if these regions were foreign antigens. This demyelination process is damaging to the electrical conductivity of neurons. The current medicines are only capable of fighting off the symptoms of the disease, but not the disease itself. Specialized stem cells, known as mesenchymal stem cells (MSCs), seem to be the candidate therapy to get rid of MS. MSCs can be isolated from multiple sources of the person's body, and even from the umbilical cord (UC) and placenta of a donor. These cells have anti-inflammatory effects so they can target the overactivity and self-antigen attacks by T cells and macrophages; this immune system overactivity is characteristic of MS. MSCs show the ability to locate into brain lesions when injected and thus can compensate for the loss of the brain function by differentiating into neuronal precursor cells and glial cells. The author has listed tables of clinical trials that have utilized MSCs from different sources, along with the years and the phase of study completed for each trial. The consensus is that these cells work on inhibiting CD4⁺ and CD8⁺ T cell activation, T regulatory cells (Tregs), and macrophage switch into the auto-immune phenotype. The best source of MSCs seems to be the UC due to the easiness of extraction, the noninvasive method of collection, their higher expansion ability and more powerful immune-modulating properties compared to other locations in the body. Studies showed there was a significant decline of mRNA expression of several cytokines after the administration of MSCs derived from the UC (UCMSCs). Other researchers were able to repair the defects of Tregs in MS patients by co-culturing Tregs from these patients with UCMSCs, which decreased the production of the pro-inflammatory cytokine IFN $γ$ , and also suggested a strong link between Tregs lack of functionality in MS patients with the pathogenesis of the disease.

Keywords: Hematopoietic stem cells; Mesenchymal stem cells; Multiple sclerosis; Regenerative medicine; Stem cell therapy.

Publication types

Review