Mesenchymal stem cells (MSCs) play a multifaceted and increasingly important role in the therapy of multiple sclerosis (MS), a chronic autoimmune disease characterized by the immune system attacking the protective myelin sheath around nerve fibers in the central nervous system. This damage leads to impaired nerve signal transmission, resulting in symptoms such as muscle weakness, coordination problems, fatigue, and cognitive difficulties. Unlike conventional treatments that mainly focus on suppressing the immune system to slow disease progression, MSCs offer a unique therapeutic potential by combining immune modulation, neuroprotection, and tissue repair.
MSCs are multipotent stromal cells capable of differentiating into various cell types, including bone, cartilage, and fat cells. They are found in multiple tissues such as bone marrow, adipose tissue, umbilical cord, and dental pulp. Their therapeutic appeal in MS stems from their ability to influence the immune system and promote regeneration without the risks associated with embryonic stem cells. MSCs exhibit a strong safety profile and can be expanded in the laboratory to obtain sufficient numbers for treatment.
One of the primary roles of MSCs in MS therapy is **immune modulation**. MS is driven by an aberrant immune response where immune cells attack the myelin sheath. MSCs can suppress the activation and proliferation of various immune cells, including T cells, B cells, dendritic cells, and macrophages. They promote the generation of regulatory T cells (Tregs), which help maintain immune tolerance and reduce inflammation. MSCs also polarize macrophages towards an anti-inflammatory M2 phenotype, further dampening harmful immune activity. This immunomodulatory effect helps reduce the ongoing damage to nerve cells and myelin.
In addition to modulating the immune response, MSCs secrete a wide array of **neurotrophic factors**—molecules that support neuron survival, growth, and repair. These factors include brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF). By releasing these substances, MSCs create a supportive environment that encourages the repair of damaged neurons and the regeneration of myelin by oligodendrocytes, the cells responsible for producing myelin in the central nervous system.
Another crucial function of MSCs in MS therapy is their ability to **promote remyelination**. Remyelination is the process of restoring the myelin sheath around nerve fibers, which is essential for normal nerve function. MSCs can enhance the recruitment and differentiation of oligodendrocyte precursor cells (OPCs) to sites of injury, facilitating the repair of damaged myelin. This regenerative capacity is vital because once myelin is lost, nerve conduction slows or stops, leading to neurological deficits.
MSCs also exhibit **anti-inflammatory and cytoprotective properties**. They reduce the production of pro-inflammatory cytokines and reactive oxygen species, which are harmful molecules that contribute to tissue damage in MS. By neutralizing these factors, MSCs protect neurons and glial cells from further injury. Moreover, MSCs can inhibit a process called NETosis, which involves the release of neutrophil extracellular traps that exacerbate inflammation.
The source of MSCs can influence their therapeutic effectiveness. For example, adipose-derived MSCs have shown promising results in promoting myelin repair and modulating immune responses. However, MSCs obtained from patients with MS may have reduced immunomodulatory capacity compared to those from healthy donors. Strategies such as pre-treating MSCs with anti-inflammatory cytokines like interleukin-10 (IL-10) can enhance their therapeutic potential by reducing their pro-inflammatory tendencies.
In clinical settings, MSCs can be administered through various routes, including intravenous infusion and intrathecal injection (directly into the cerebrospinal fluid). These delivery methods aim to maximize the cells’ ability to reach the central nervous system and exert their beneficial effects. Unlike hematopoie
