#2730 MESENCHYMAL STEM CELLS FOR THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS WITH NEPHRITIS

Abstract

Abstract Background and Aims Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease of unknown aetiology affecting various organs and tissues. In the last decade, alternative therapeutic methods for SLE refractory to immunosuppressive therapy have been actively studied. Of interest are the data of transplantation of mesenchymal stem cells (MSCs) that demonstrated immunomodulatory properties, as well as the ability to self-renewal and multi-lineage differentiation. Objective to evaluate the efficacy and safety of MSCs in patients with severe refractory SLE. Method The search was conducted on PubMed and Google Scholar platforms using the following strategy: “Systematic lupus erythematosus” plus “Mesenchymal stem cells”. All articles presented in these domains published before 01.12.2022 in the format of case reports, clinical studies, clinical trials, multicentre studies were analysed. The effectiveness of MSCs was evaluated using the systemic lupus erythematosus activity index SELENA-SLEDAI, renal functional parameters (daily proteinuria, creatinine, glomerular filtration rate (GFR), and serum albumin), immunological parameters (anti-nuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA). The safety assessment included registration of various adverse events during and after transplantation. Results A total of 201 publications were retrieved for the period from 2000-2022, and 24 records about MSCs treatment in SLE patients met the above criteria and were included in the study. The analysed publications included data on the transplantation of MSCs obtained from various biological sources such as bone marrow, adipose tissue, and umbilical cord. In total, the results of MSCs transplantations in 806 patients were analysed. The average age of patients was 30.5±8.53 years old (from 12 to 62 years). The results obtained suggested that there was a significant decrease in the activity of SLE: 2.5-fold reduce in SELENA-SLEDAI score after 12 months (from 12.43±3.06 to 5.02±2.12). Anti-dsDNA titer dropped from 399.05±477.86 to 227.65±130.76. Some research also revealed decrease in ANA titer from 309.64±412.75 to 187.8±146.60. The improvement of kidney function was assessed by the 2.17-fold reduction of daily proteinuria from 2.48±0.66 to 1.14±0.56 g/l and an increase in GFR from 66.84±42.2 to 83.25±44.90 ml/min. Furthermore, in the majority of the cases of SLE patients who had been treated with conventional immunosuppressants and glucocorticoids with no response, the dosage of immunosuppressive therapy after MSCs transplantation was reduced. The safety of MSCs therapy is essential for clinical application. The assessment of all patients (n = 806) who underwent MSCs transplantation revealed a few side effects such as nausea (n = 7), herpes (n = 2), agranulocytosis with fungal pneumonia (n = 2), tuberculosis (n = 3). No tumor-related events was observed. Mortality consists in 2.6%, the majority of cases was from multiple organ failure (n = 19), others - from acute heart failure (n = 1) and severe pneumonia (n = 1). Thus, the survival rate during MSCs transplantation consists in 97.4%. Conclusion According to the analysis of currently available research data MSCs demonstrated a significant therapeutic effect in SLE with kidney injury: the decrease in the activity index SELENA-SLEDAI, the improvement in kidney function and the decrease in immunological indicators. According to the data from follow-up studies there were no serious adverse events, or tumor-related effects after MSCs transplantation in SLE patients.