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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. Therefore, this study compared the therapeutic outcomes of four approaches; bone marrow-derived mesenchymal stem cells (BM-MSCs), their conditioned media (CM), BM-MSCs pre-conditioned with NaHS, and their conditioned media in a rat model of adjuvant-induced polyarthritis. The process involved the isolation of MSCs from rat bone marrow, propagation, and characterization of the isolated cells. polyarthritis was induced in male\n                    <jats:italic>Wistar<\/jats:italic>\n                    rats via intradermal injection of type II collagen on day 0 and day 21. Affected rats were treated with naproxen, BM-MSCs, BM-MSCs-CM, NaHS, BM-MSCs preconditioned with NaHS, or BM-MSCs preconditioned with NaHS-CM. The results indicated that the administered cells homed to the bone marrow and bone trabeculae of the knee joint tissue of the afflicted rats. The proposed treatments brought about significant down-regulation of peptidyl arginine deiminase 2 (PAD2) and chemokine ligand 13 (CXCL13) genes as well as angiopoietin-1 (Ang-1) protein expression, along with substantial upregulation of the galectin-1 (GAL-1) gene and osteoprotegerin (OPG) protein expression. Compared with BM-MSCs therapy, the treatment with BM-MSCs preconditioned with NaHS and their CM exhibited superior effect, with values close to those of the controls. In addition, treatment with the CM of BM-MSCs offered a lesser effect compared to BM-MSCs therapy alone. In conclusion, NaHS has the potential to improve the therapeutic capability of BM-MSCs for RA in rats by enhancing their anti-inflammatory, immunomodulatory, and regenerative capacity.\n                  <\/jats:p>","DOI":"10.1007\/s10787-025-02078-1","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:11:03Z","timestamp":1766049063000},"page":"399-418","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hydrogen sulphide modifies the therapeutic potential of bone marrow mesenchymal stem cells in an adjuvant-induced polyarthritis rat model through the mitigation of angiogenesis, ectopic lymphoid tissue formation, and osteoclastogenesis"],"prefix":"10.1007","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4305-5893","authenticated-orcid":false,"given":"Sara M.","family":"El-Sayed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9269-3128","authenticated-orcid":false,"given":"Mohamed R.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2204-6627","authenticated-orcid":false,"given":"Mohamed M.","family":"Naguib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0837-0172","authenticated-orcid":false,"given":"Hadeer A.","family":"Aglan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8642-9251","authenticated-orcid":false,"given":"Hanaa H.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"2078_CR2","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1111\/1440-1681.13240","volume":"47","author":"ESH Abd Allah","year":"2020","unstructured":"Abd Allah ESH, Ahmed MA, Makboul R, Abd El-Rahman MA (2020) Effects of hydrogen sulphide on oxidative stress, inflammatory cytokines, and vascular remodelling in l-NAME-induced hypertension. 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