{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:50:54Z","timestamp":1785433854405,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi"},{"id":[{"id":"https:\/\/ror.org\/024ghrf67","id-type":"ROR","asserted-by":"publisher"}]},{"name":"\u00c5ke Wibergs Stiftelse"},{"id":[{"id":"https:\/\/ror.org\/03htnqd27","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Inhibition of Wnt\/\u03b2-catenin signaling differentiates mesenchymal stem cells (MSCs) into hepatocytes. However, there is lack of data on whether transplanting these cells can enhance liver regeneration. Additionally, it remains unknown if the flavonoids quercetin and rutin and the clinically used drug lithium chloride (LiCl) can effectively differentiate MSCs into hepatocytes and promote liver regeneration. To address this, the rat bile duct ligation (BDL) fibrosis model was used. Male Wistar rats were surgically ligated. Liver function tests, histological analysis and cell tracking were also conducted to validate liver regeneration. Treatment with quercetin inhibited the Wnt pathway, while rutin and LiCl activated it. Hepatic differentiation was noted in three treatment groups: quercetin, quercetin with rutin and LiCl. We observed that the initial downregulation of the Wnt pathway, followed by its upregulation, facilitated the differentiation of MSCs into hepatocytes. Transplantation of quercetin-treated MSC-derived hepatocytes into the rat BDL fibrosis model resulted in complete restoration of liver function, normalization of elevated systemic liver enzymes and reduction of inflammation and fibrosis. Interestingly, quercetin-treated hepatocytes resulted in enhanced liver regeneration compared to rutin and LiCl. Finally, tracking of labeled hepatocytes confirmed their main localization in the liver. In conclusion, MSC-derived hepatocytes, generated through ex vivo treatment with quercetin, exhibit enhanced liver regeneration. These findings provide a novel ex vivo treatment strategy with flavonoids and the clinically used drug LiCl to achieve enhanced liver regeneration in vivo.<\/jats:p>","DOI":"10.3390\/cells15131206","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T10:04:44Z","timestamp":1782986684000},"page":"1206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transplantation of Mesenchymal Stem Cell-Derived Hepatocytes Primed with Quercetin Alone or in Combination with Rutin and LiCl Enhances Liver Regeneration"],"prefix":"10.3390","volume":"15","author":[{"given":"Tuba Shakil","family":"Malick","sequence":"first","affiliation":[{"name":"Stem Cell Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0458-0263","authenticated-orcid":false,"given":"Rida-E-Maria","family":"Qazi","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"},{"name":"Centre for Regenerative Medicine and Stem Cell Research, The Aga Khan University Karachi, Karachi 74800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Ishaque","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"},{"name":"College of Molecular Medicine, Ziauddin University, Karachi 75600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9991-1669","authenticated-orcid":false,"given":"Abiha","family":"Fatima","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1878-7836","authenticated-orcid":false,"given":"Irfan","family":"Khan","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"},{"name":"Centre for Regenerative Medicine and Stem Cell Research, The Aga Khan University Karachi, Karachi 74800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1743-051X","authenticated-orcid":false,"given":"Shaheen","family":"Faizi","sequence":"additional","affiliation":[{"name":"HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5181-0458","authenticated-orcid":false,"given":"Asmat","family":"Salim","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1832-1051","authenticated-orcid":false,"given":"Farasat","family":"Zaman","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Karolinska Institute, Biomedicum A4, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. 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