Sara ElSayed Reda

Egypt

Preconditioning of bone marrow mesenchymal stem cells with sodium hydrosulfide enhances their therapeutic potential in CIA rat model

Sara M. El-Sayeda, Hanaa H. Ahmedb,c, Hadeer A. Aglanb,c, Mohamed M. Naguiba, Mohamed R. Mohameda*

aBiochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
bHormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt.
cStem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt.

Abstract

Background

Among the chronic and progressive autoimmune disorders that primarily affect joints in the hands, wrists, and knees, rheumatoid arthritis (RA) is a highly prevalent one. A significant number of patients develop severe adverse events, display weak responses, or cannot afford long-term use of the current RA medications, requiring more efficient and safer curative alternatives. increasing evidence recommends the application of mesenchymal stem cells (MSCs)-based therapy for mitigating chronic inflammation and boosting tissue renewal in intractable disorders. Moreover, sodium hydrosulphide (NaHS) has recently been found to have anti-inflammatory effects.

Methods

MSCs were isolated and cultured from rat bone marrow, and their characteristics were determined. The CIA model was induced in rats by intradermal injections of type II collagen on days 0 and 21. A variety of treatments were administered, including naproxen, BM-MSCs, BM-MSC-conditioned media, NaHS, BM-MSCs preconditioned with NaHS, and BM-MSCs preconditioned with NaHS-conditioned media.

Results

The outcomes demonstrated that untreated CIA rats exhibited severe joint pathology. Behaviorally, they showed abnormal walking patterns . Biochemically, there was a significant increase in serum inflammatory markers . Molecular analysis revealed significant upregulation of synovial TNF-α, PAD2 and CXCL13 mRNA and MMP-1 and Ang-1 protein expression levels along with a significant down regulation of the GAL-1 gene and OPG protein expression levels . Treatment with proposed agents, including BM-MSCs, resulted in histological refinement, normalized proteoglycan levels, significant reductions in gait score and PWF, and a decrease in serum inflammatory markers. Molecularly, treatments downregulated TNF-α, PAD2 and CXCL13 mRNA levels , MMP-1 and Ang-1 protein expression levels, and upregulation of GAL-1 gene and OPG protein expression.

Conclusions

This study concludes that NaHS enhances the therapeutic efficacy of BM-MSC therapy for RA by augmenting their anti-inflammatory, immunomodulatory, and regenerative properties.