{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:04:47Z","timestamp":1783537487402,"version":"3.55.0"},"reference-count":65,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Doxorubicin (DOX) is widely used to treat a variety of malignancies in both adults and children, including those of the bladder, breast, stomach, and ovaries. Despite this, it has been reported to cause hepatotoxicity. The recent discovery of bone marrow-derived mesenchymal stem cells\u2019 (BMSCs) therapeutic effects in the context of liver diseases suggests that their administration plays a part in the mitigation and rehabilitation of drug-induced toxicities. Objectives: This study investigated whether bone BMSCs could reduce DOX-induced liver damage by blocking the Wnt\/\u03b2-catenin pathway that causes fibrotic liver. Materials and methods: BMSCs were isolated and treated with hyaluronic acid (HA) for 14 days before injection. Thirty-five mature male SD rats were categorized into four groups; group one (control) rats were supplemented with saline 0.9% for 28 days, group two (DOX) rats were injected with DOX (20 mg\/kg), group three (DOX + BMSCs) rats were injected with 2 \u00d7 106 BMSCs after 4 days of DOX injection, group four (DOX + BMSCs + HA) rats were injected with 0.1 mL BMSCs pretreated with HA after 4 days of DOX. After 28 days the rats were sacrificed, and blood and liver tissue samples were subjected to biochemical and molecular analysis. Morphological and immunohistochemical observations were also carried out. Results: In terms of liver function and antioxidant findings, cells treated with HA showed considerable improvement compared to the DOX group (p &lt; 0.05). Moreover, the expression of inflammatory markers (TGF\u03b21, iNos), apoptotic markers (Bax, Bcl2), cell tracking markers (SDF1\u03b1), fibrotic markers (\u03b2-catenin, Wnt7b, FN1, VEGF, and Col-1), and ROS markers (Nrf2, HO-1) was improved in BMSCs conditioned with HA in contrast to BMSCs alone (p &lt; 0.05). Conclusion: Our findings proved that BMSCs treated with HA exert their paracrine therapeutic effects via their secretome, suggesting that cell-based regenerative therapies conditioned with HA may be a viable alternative to reduce hepatotoxicity.<\/jats:p>","DOI":"10.3390\/cells12111526","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T01:40:56Z","timestamp":1685583656000},"page":"1526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hepatoprotective Effects of Hyaluronic Acid-Preconditioned Bone Marrow Mesenchymal Stem Cells against Liver Toxicity via the Inhibition of Apoptosis and the Wnt\/\u03b2-Catenin Signaling Pathway"],"prefix":"10.3390","volume":"12","author":[{"given":"Amira","family":"Awadalla","sequence":"first","affiliation":[{"name":"Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman T.","family":"Hamam","sequence":"additional","affiliation":[{"name":"Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5880-8630","authenticated-orcid":false,"given":"Sally Abdallah","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seham Ahmed","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2687-6735","authenticated-orcid":false,"given":"Khalid Mohamed","family":"Elazab","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Jazan University, Jazan 82511, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Mohamed","family":"El Nakib","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6589-4514","authenticated-orcid":false,"given":"Mamdouh","family":"Eldesoqui","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"},{"name":"Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-1743","authenticated-orcid":false,"given":"Mohamed","family":"El-Sherbiny","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9377-6462","authenticated-orcid":false,"given":"Omar A.","family":"Ammar","sequence":"additional","affiliation":[{"name":"Basic Science Department, Delta University for Science and Technology, Gamasa 35712, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2121-9269","authenticated-orcid":false,"given":"Rasha Hamed","family":"Al-Serwi","sequence":"additional","affiliation":[{"name":"Department of Basic Dental Sciences, College of Dentistry, Princess Nourahbint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6405-6033","authenticated-orcid":false,"given":"Mohamed A.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira","family":"Sarhan","sequence":"additional","affiliation":[{"name":"Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4105-776X","authenticated-orcid":false,"given":"Mohamed","family":"Ali","sequence":"additional","affiliation":[{"name":"Biochemistry Division, Chemistry Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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