{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:53:10Z","timestamp":1790610790204,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T00:00:00Z","timestamp":1631923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"publisher","award":["R.G.P.1\/171\/42"],"award-info":[{"award-number":["R.G.P.1\/171\/42"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Autophagy is a key metabolic process where cells can recycle its proteins and organelles to regenerate its own cellular building blocks. Chemotherapy is indispensable for cancer treatment but associated with various side-effects, including organ damage. Stem cell-based therapy is a promising approach for reducing chemotherapeutic side effects, however, one of its main culprits is the poor survival of transplanted stem cells in damaged tissues. Here, we aimed to test the effects of activating autophagy in adipose-derived mesenchymal stem\/stromal cells (ADSCs) on the survival of ADSCs, and their therapeutic value in cisplatin-induced liver injury model. Autophagy was activated in ADSCs by rapamycin (50 nM\/L) for two hours before transplantation and were compared to non-preconditioned ADSCs. Rapamycin preconditioning resulted in activated autophagy and improved survival of ADSCs achieved by increased autophagosomes, upregulated autophagy-specific LC3-II gene, decreased protein degradation\/ubiquitination by downregulated p62 gene, downregulated mTOR gene, and finally, upregulated antiapoptotic BCL-2 gene. In addition, autophagic ADSCs transplantation in the cisplatin liver injury model, liver biochemical parameters (AST, ALT and albumin), lipid peroxidation (MDA), antioxidant profile (SOD and GPX) and histopathological picture were improved, approaching near-normal conditions. These promising autophagic ADSCs effects were achieved by modulation of components in TGF-\u03b21\/Smad and PI3K-AKT signaling pathways, besides reducing NF-\u03baB gene expression (marker for inflammation), reducing TGF-\u03b21 levels (marker for fibrosis) and increasing SDF-1 levels (liver regeneration marker) in liver. Therefore, current results highlight the importance of autophagy in augmenting the therapeutic potential of stem cell therapy in alleviating cisplatin-associated liver damage and opens the path for improved cell-based therapies, in general, and with chemotherapeutics, in particular.<\/jats:p>","DOI":"10.3390\/cells10092475","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T07:52:14Z","timestamp":1632124334000},"page":"2475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Autophagy Promotes the Survival of Adipose Mesenchymal Stem\/Stromal Cells and Enhances Their Therapeutic Effects in Cisplatin-Induced Liver Injury via Modulating TGF-\u03b21\/Smad and PI3K\/AKT Signaling Pathways"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2883-6761","authenticated-orcid":false,"given":"Eman Mohamad","family":"El Nashar","sequence":"first","affiliation":[{"name":"Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia"},{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6613-1498","authenticated-orcid":false,"given":"Mansour Abdullah","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia"},{"name":"Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wardah Abdullah","family":"Alasmari","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, Makkah 24230, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5322-3860","authenticated-orcid":false,"given":"Mohamed M. A.","family":"Hussein","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0064-7835","authenticated-orcid":false,"given":"Eman","family":"Hamza","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"},{"name":"Department of Biochemistry and Molecular Biology, Horus University, Damietta 34511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3212-6567","authenticated-orcid":false,"given":"Reham Ismail","family":"Taha","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona M.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khulood Mohammed","family":"Al-Khater","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3478-1098","authenticated-orcid":false,"given":"Ahmed","family":"Abdelfattah-Hassan","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt"},{"name":"Biomedical Sciences Program, Zewail City of Science and Technology, University of Science and Technology, Giza 12578, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. 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