Impact of the therapy that changes the clinical course of multiple sclerosis using allogeneic mesenchymal stem cell transplantation on the immunological parameters of patients
Authors: Fedulov A. S. , Zafranskaya M. M. , Borisov A. V. , Nizhegorodova D. B. , Volkova N. A. , Krivenko S. I. , Shalukho T. A. 
Published: December 2023

Multiple sclerosis (MS) is a multifactorial, autoimmune, chronic disease of the nervous system, manifested by multifocal neurological symptoms and occurring in typical cases in the presence of symptoms of a relapsing course. MS is one of the problems of modern neurology, which is characterized by the prevalence of diseases, the prevalence of patients in the age group from 20 to 40 years, as well as high disability. The main target of therapeutic options in MS is the appearance  on the immune system in order to suppress the inflammatory process leading to demyelination. With a set of drugs that allow clinically modifying the course of MS (beta-interferon, glatiramer acetate, fingolimod, etc.), 40 % of patients have a good effect, 40 % have a questionable result, and 20 % of patients with MS do not detect treatment. Lack of treatment protocols aimed at selective stimulatory suppression of autoreactive T-lymphocyte clones and restoration of affected areas of the CNS, weakening of the ever-increasing interest in identifying the immunomodulatory and neuroprotective properties of mesenchymal stem cells (MSCs). From carriers, the benefits of allogeneic versus autologous MSC implantation are widely discussed without the presence of objective evidence of the superiority of one type of cell therapy over the estimated and estimated fees of autologous or allogeneic transplants in obtaining MS remains controversial.

Objective ‒ to study the effect of modifying therapy using allogeneic mesenchymal stromal stem cells on the immunological parameters of patients with multiple sclerosis.

The results of assessing the dynamics of a number of immunological biomarkers in 4 patients with relapsing-remitting MS. All patients are men. The median age is 35.0 + 11.4 years. At the screening period, the Expanded Disability Status Scale (EDSS) score was 3.6 [2.5; 6.0]. immunological and cellular-morphological parameters of MSC cultures were revealed, enhanced due to adipose tissue (AT) of 7 donors. Of the 7 samples of AT MSCs, 2 samples were selected with the highest coefficients of suppression of T-lymphocyte proliferation, of which 4 biomedical cell products should be taken for therapy.

In patients with MS, the most significant changes were observed by 6 months of the post-transplantation period and were characterized by a decrease in γIFN production, the number of functions of immature “double positive” and “double negative” T-lymphocytes, and a decrease in the cytotoxic orientation of T-lymphocytes with a γδ T-cell receptor characterized by characteristics of an increase in the number of cells expressing CD45RO+ (memory cell marker) in an increase with a decrease in the number of γδTCR CD314+ lymphocytes (expressive key activator of killer receptors).

Preliminary results from a study of transplantation of alloMSCs to the immunological status of MS patients suggest that they accept disease-modifying therapy in this application as pathogenetic, disease-modifying therapy.