Long‐term passages of human clonal mesenchymal stromal cells can alleviate the disease in the rat model of collagen‐induced arthritis resembling early passages of different heterogeneous cells

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of unknown cause. The interaction of immune system cells and the secretion of inflammatory cytokines with synovial cells leads to severe inflammation in the affected joints. Currently, medications, including non‐steroidal anti‐inflammatory drugs, glucocorticoids, and more recently, disease‐modifying anti‐rheumatic drugs, are used to reduce inflammation. However, long‐term use of these drugs causes adverse effects or resistance in a considerable number of RA patients. Recent findings revealed the safety and efficacy of mesenchymal stromal cells (MSCs)‐based therapies both in RA animal models and clinical trials. Here, the beneficial effects of bone marrow‐derived heterogeneous MSCs (BM‐hMSCs) and Wharton jelly‐derived MSCs (WJ‐MSCs) at early passages were compared to BM‐derived clonal MSCs (BM‐cMSCs) at high passage number on a rat model of collagen‐induced arthritis. Results showed that systemic delivery of MSCs significantly reversed adverse changes in body weight, paw swelling, and arthritis score in all MSC‐treated groups. Radiological images and histological evaluation demonstrated the therapeutic effects of MSCs. There was a decrease in serum level of anti‐collagen type II immunoglobulin G and the inflammatory cytokines interleukin (IL)‐1β, IL‐6, IL‐17, and tumor necrosis factor‐α in all MSC‐treated groups. In contrast, an increase in inhibitory cytokines transforming growth factor‐β and IL‐10 was seen. Notably, the long‐term passages of BM‐cMSCs could alleviate RA symptoms similar to the early passages of WJ‐MSCs and BM‐hMSCs. The importance of BM‐cMSCs is the potential to establish cell banks with billions of cells derived from a single donor that could be a competitive cell‐based therapy to treat RA.

WITHDRAWN: Effects of ethyl acetate fraction ofPsychotria vogelianaleaf on liver function, kidney function, and cytokines level of induced rheumatoid arthritis in albino rats

“…A classic experimental animal model of human rheumatoid arthritis, complete Freund's adjuvantinduced rheumatoid arthritis is widely used to explore anti-arthritic drugs. The mouse model of arthritis produced by collagen antibodies is one of the other models 26 , pristine-induced arthritis 27 , rat collagen-induced arthritis 28 and Collagen Type II Induced Arthritic 29 . Animals vaccinated with CFA have been reported to have a significant inflammatory response following the inoculation which can lead to substantial joint remodelling and edoema 30 .…”

“…; https://doi.org/10.1101/2024.03. 28.587315 doi: bioRxiv preprint Medication used to control and decrease inflammatory crises includes immunosuppressants, steroids, and nonsteroid anti-inflammatory medicines; however, these drugs are costly and have deleterious effects 8 . Many plant components, including leaves, stems, bark, roots, and so forth, are employed in order to prevent, relieve, or return anomalies to normal 9 .…”

Rheumatoid arthritis: the old issue, the new therapeutic approach

“…Our study revealed a significant decrease in specific IgG levels autoantibodies across all three MSC treatment groups compared to the sham group. This provides strong evidence for the ability of MSCs to reduce serum levels of autoreactive antibodies against CII, specifically CII-specific IgG, and to modulate humoral-specific immune responses against it [ 21 ].…”

“…Various preclinical studies have extensively investigated the use of MSCs in tissue repair, yielding encouraging results [ 34 ]. In addition to their capability for tissue regeneration, the immunomodulatory effects of MSCs have been proven in various studies [ 21 , 35 , 36 ]. These properties of MSCs have led to their use in the treatment of autoimmune diseases and graft versus host disease (GvHD) in recent decades with promising results [ 37 ].…”

“…The results showed that MSCs significantly reversed adverse changes in body weight, paw swelling, and arthritis score in all MSC-treated groups. Radiological images and histological evaluation demonstrated the therapeutic effects of MSCs [ 21 ].…”