Tolerogenic CT of autoimmune diseases is based on correcting immune-related disorders accumulated in the patient’s body, where stable remission, independent of medication, can be achieved.

In patients with SLE, the long-term anti-inflammatory, immunosuppressive, and antifibrotic effects of MSCs restore the balance of immunocompetent cells and the activity of Tregs, which oversee autoimmune diseases.

It also ensures the removal of autoreactive memory T cells and the regeneration of a normally functioning immune system with a predominance of «native» B-cells without signs of autoreactivity, essentially «rebooting» the immune system from a chronic autoreactive to a normal autotolerant status.

MSCs obtained from patients with systemic inflammatory diseases, including SLE, have an aberrant phenotype, atypical morphology, and are characterized by low proliferative and immunosuppressive activity.

Therefore, for CT of SLE, BMCPs based on pooled allogeneic MSCs obtained from OE of several (at least three) healthy donors are used.

Pooled MSCs possess more pronounced and stable immunomodulatory properties compared to MSCs obtained from a single donor, and even more so compared to the patient’s own MSCs compromised by autoimmune pathology.

The low immunogenicity of pooled MSCs allows their use without matching donor-recipient pairs.

Treatment Scheme

CT of SLE is conducted on an outpatient basis and involves a single administration of BMCP in the day hospital ward of the CTD.

BMCP based on pooled MSCs is administered intravenously in a dose of 1.0×10⁶ cells per 1 kg of the patient’s body weight using a syringe pump at an infusion rate of 60 ml/h.

In case of clinical effectiveness after the first BMCP administration, repeated cell transplantations may be performed during subsequent SLE exacerbations.

Effectiveness

The clinical effectiveness of CT is indicated by a decrease in the SELENA-SLEDAI index and the achievement of clinical-laboratory remission based on the dynamics of immunological blood parameters (antibodies to double-stranded DNA, antinuclear antibodies, C3 and C4 complement components).

The success of CT correlates with the severity of morphological damage and the functional state of the kidneys, with nephrosclerosis and renal failure being predictors of ineffectiveness.

CT of SLE is applied not only as an adjunct to medication treatment strategies but also as a method that changes the pathogenetic course of SLE and slows its progression, capable of controlling multi-organ manifestations of symptoms.

The severity and duration of the clinical effect are determined by the type of SLE course and the degree of target organ damage: high progression rates of SLE and severe irreversible tissue damage make the prognosis of cell therapy unfavorable.

Safety and Complications

The safe use of donor MSCs is possible due to the absence of major histocompatibility complex (human leukocyte antigen — HLA) type II molecules on the cell surface and almost complete absence of HLA type I.

The organization of virological control during the production of certified BMCPs according to global GMP standards ensures the virological purity of donor pooled MSCs and excludes recipient infection.

There is a possibility of altered susceptibility to bacterial and viral infections due to immunosuppression, which also potentially increases the risk of carcinogenesis, especially if there is an undiagnosed tumor process.