Multiple sclerosis (MS) is a rare, incurable disease that is autoimmune in nature and degenerative to the central nervous system. The disease can take on many courses, affected by many known (and unknown) factors, but the definite involvement of the adaptive immune system in its pathophysiology has focused the minds of researchers to create drugs that target this system. The goal is to modulate the immune system in a way that reduces inflammatory processes while limiting neuronal and axonal damage.
Currently, there are many disease-modifying therapies (DMTs) available, all of which are characterized by their immunomodulatory function. The main drawback, besides their relative newness, is that they tend to cause adverse effects, some of which are reported to be severe. Current DMTs also require life-long use.
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Cell-based therapies could potentially replace DMTs as the preferred choice of MS medication, as they have the potential to lower morbidity by reducing adverse effects and hospital admissions. A group of researchers from Antwerp University Hospital in Belgium conducted a review of cell-based therapies that are currently being developed and published their findings in the International Journal of Molecular Sciences. We will take a look at some of these promising cell-based therapies in this article.
Hematopoietic Stem Cells
The therapeutic potential of hematopoietic stem cells (HSCs) lies in the fact that they can be developed into all types of blood cells. The goal, therefore, is to be able to give a one-off HSC transplantation to MS patients that can provide for long-term disease stabilization. HSC transplantation supports hematopoiesis, which allows the immune system to be replenished and renewed.
HSCs are usually harvested from the bone marrow. MS, being an autoimmune disease, is usually treated with autologous HSC transplants out of an abundance of caution. Autologous HSC transplantation is also a rescue treatment in young patients with relapsing-remitting MS who are known to have an aggressive inflammatory disease course. A study indicated that a very high proportion of patients who received that treatment achieved no evidence of disease activity compared to patients who received DMTs.
How does autologous HSC transplantation achieve such radical results in MS patients? Researchers are still unsure of its exact mechanism of action, but the immunological changes that this procedure triggers in the body suggest that it works by inducing long-term immune tolerance. In any case, it is a well-proven treatment option for young patients with relapsing-remitting MS who fail to respond to DMTs.
Mesenchymal Stromal Cells
Mesenchymal stromal cells (MSCs) have the ability to differentiate into different kinds of tissue of mesodermal origin. They are, in other words, multipotent. MSCs can be isolated from different parts of the body, including the blood, bone marrow, adipose tissue, and skeletal muscle. Quantities obtained from primary tissues are insufficient for clinical use; hence, in vitro propagation is needed to achieve sufficient quantities for in vivo use.
MSCs have gained interest over the years due to their immunosuppressive and anti-inflammatory properties, which have been demonstrated both in vitro and in vivo. Their exact mechanisms of action are unknown, but they have been observed to turn the inflammatory environment in MS and other autoimmune diseases into one that is noninflammatory.
Studies found that MSCs are safe and well tolerated by MS patients. In addition to their immunosuppressive actions, researchers found that they are likely to also confer neuroprotective benefits. However, their migratory potential and homing capacity into the central nervous system still deserve more research.
Regulatory T Cells
Regulatory T cells (Tregs) are a subset of CD4+ T cells that are defined by a study as “a heterogenous mixture of cellular subphenotypes with a high degree of phenotypic complexity that reflected different states of maturation, differentiation, and activation.”
They work by suppressing, inactivating, or eliminating effector T cells in the periphery, thus maintaining tolerance to self and minimizing self-damage during persistent immunity. Studies suggested that the impairment of Tregs increases the risk of autoimmune diseases such as psoriasis, myasthenia gravis, and of course, MS. Hence, the action of Tregs that suppresses autoimmunity could be instrumental in treating these diseases.
The potential use of Tregs in fighting autoimmune diseases has resulted in more than 50 active or completed clinical trials at the time of publishing. In addition, Tregs can also potentially be used to prevent graft rejection. We still do not know much about how Tregs affect the body in the long term; a study suggested that polyclonal Tregs can result in a transient risk of generalized immunosuppression. However, the sheer volume of ongoing clinical trials should provide us with much-needed information about this therapy soon.
Tolerogenic Dendritic Cells
Dendritic cells (DCs) provide the crucial link between the innate and adaptive systems; they play a critical role in balancing immunity and tolerance. They simultaneously capture self-antigens and exogenous antigens in the peripheral tissues and present them to other immune cells, as well as stimulate the production of immune cells.
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Various clinical trials recommended the use of immune-stimulatory DCs to boost immunity in cancer and infectious diseases, but the use of tolerogenic DCs in autoimmune diseases is still fairly new. A small number of studies used tolerogenic DCs to treat patients with diseases such as type 1 diabetes, rheumatoid arthritis, MS, and Crohn’s disease. Researchers are still investigating the safety and tolerability of tolerogenic DCs for use in patients with MS, but ongoing studies should yield fascinating new insights soon.
These cell-based therapies, as well as others not mentioned in this article, give MS patients reasons for optimism. It may very well be that the future of MS treatment will become more simplified, more effective, and longer lasting.
“Ongoing and future studies will help to define the dose, treatment schedule, and route of administration of antigen-specific cell therapy in patients with MS regarding safety, efficacy, and treatment-related costs,” the authors of this study concluded.
Wens I, Janssens I, Derdelinckx J, Meena M, Willekens B, Cools N. Made to measure: patient-tailored treatment of multiple sclerosis using cell-based therapies. Int J Mol Sci. Published online July 14, 2021. doi:10.3390/ijms22147536
Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. Published online January 4, 2020. doi:10.1056/NEJMra1401483