Autoimmune diseases occur as a result of a malfunction of the body’s immune system, which leads to the production of antibodies to healthy tissues. The defeat of a certain type of tissue determines the clinical picture of a particular autoimmune disease. In addition, immune disorders lead to an internal conflict in the body and the absorption of antibodies produced in response to other diseases by autoimmune antibodies.
The development of autoimmune diseases leads to severe damage to internal organs and systems, and as a result, to a fatal deterioration in human health, up to a deep disability of the patient and death.
Causes and treatment of autoimmune diseases
The main causes of autoimmune diseases are congenital disorders, or infections that have already been transferred, which caused an imbalance or replacement of antibodies or their parts, as well as tissue necrosis, hyperimmunity (a pathological increase in the number of antibodies and their aggressiveness), violation of tissue barriers.
Autoimmune diseases are divided into short-term (occurring in the course of life and associated with a certain traumatic factor) and chronic, and short-term ones can become chronic. Chronic autoimmune diseases are difficult to treat, adversely affect the entire body of the patient, accompanied by various complications.
The treatment of autoimmune diseases consists in normalizing the functions of the immune system as a whole (including the suppression of hyper immunity and selectivity disorders) and an attempt, if not to completely restore damaged tissues, then at least slow down / stop degenerative processes. As part of the implementation of an integrated approach to the treatment and rehabilitation of such patients, this is done with the help of various kinds of drugs, including through methods of regenerative therapy.
The most effective method of regenerative therapy in the context of correcting the condition of patients with autoimmune disorders is currently considered to be the course use of mesenchymal stem cells (MSCs).
Regenerative therapy of autoimmune diseases using MSCs
MSCs significantly simplify the process of normalizing body functions. They have the property of homing (that is, they move around the body and invade damaged tissues) and are able to automatically, in the absence of their pathology, determine which tissues need stabilization and restoration.
To date, at least 80 autoimmune diseases are known to medicine.
In 2002, newborn umbilical cord stem cells (so-called mesenchymal stromal stem cells, MSCs) were first shown to have a strong influence on innate and acquired immune responses. It was found that MSCs inhibit the activation and proliferation (multiplication) of T- and B-lymphocytes and can affect the maturation of dendritic cells*.
What are dendritic cells?
* In 1973, Ralph Steinman discovered a new type of cell, which he called dendritic, because outwardly they resembled the dendrites (short processes) of neurons. The cells were found in all tissues of the body that came into contact with the external environment: in the skin, lungs, mucous membrane of the gastrointestinal tract. First, the researcher suggested, and then proved, that the function of dendritic cells is to present “enemy” antigens to other cells of the immune system. That is, this is the “first line of defense”, which sends a signal through them that activates T-cells and starts the cascade of antibody production by B-cells.
Recently, the immunosuppressive effects of MSCs have been studied in different directions. Studies have shown that MSCs induce the formation of anti-inflammatory macrophages and promote the differentiation of regulatory T-lymphocytes with stable immunosuppressive activity.
So in what autoimmune diseases has a positive effect of MSCs been established?
Crohn’s disease usually affects the entire gastrointestinal tract of the patient with persistent inflammation and fistula formation. The first report on the results of a phase I clinical trial on cell therapy using MSCs was published in 2005. Local injection resulted in healing of fistulas (6 out of 8 patients) without any side effects. These results were confirmed in 2009 in a phase II, multicenter, randomized, placebo-controlled study of 49 patients with complex perianal fistulas. Currently, the biotech company Mesoblast has completed a phase 3 clinical study of the effectiveness of MSCs in the treatment of 330 patients with Crohn’s disease. The results will be published soon.
Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system leading to severe disability. In the first report of a pilot study (own MSCs, epidural administration), no adverse reactions were observed in 10 patients, indicating the feasibility of using MSCs for the treatment of multiple sclerosis. A further two phase I/II studies involving 10-15 patients each confirmed the absence of side effects during follow-up (6-28 months). An increase in the proportion of regulatory T cells (inhibiting autoimmune reactions) was found just a few hours after MSC transplantation. Patients improved visual function indicators, the progression of general disability also decreased after treatment. The reproducibility and clinical significance of these results remains to be confirmed. The International Research Group on MSC Transplantation developed guidelines in 2010 for the use of MSCs in multiple sclerosis, as well as protocols for cell culture and patient management.
Systemic lupus erythematosus
The most remarkable results of MSC therapy have been obtained in clinical trials of severe treatment-refractory systemic lupus erythematosus. This disease should be considered the most severe autoimmune disease, since in this case the immune attack is directed at one’s own DNA, which is contained in almost all cells of the body.