PMID- 33479191 OWN - NLM STAT- MEDLINE DCOM- 20211004 LR - 20230919 IS - 2041-4889 (Electronic) VI - 12 IP - 1 DP - 2021 Jan 21 TI - Mesenchymal stem cells ameliorate lipid metabolism through reducing mitochondrial damage of hepatocytes in the treatment of post-hepatectomy liver failure. PG - 111 LID - 10.1038/s41419-020-03374-0 [doi] LID - 111 AB - Hepatectomy is an effective therapeutic strategy for many benign and malignant liver diseases, while the complexity of liver anatomy and the difficulty of operation lead to complications after hepatectomy. Among them, post-hepatectomy liver failure (PHLF) is the main factor threatening the life of patients. At present, liver transplantation is an effective approach for PHLF. However, the application of liver transplantation has been largely limited due to the shortage of donors and the high cost of such operation. Therefore, it is urgently necessary to develop a new treatment for PHLF. Mesenchymal stem cells (MSCs) have become a new treatment regimen for liver diseases because of their easy access and low immunogenicity. Our study found that there were some subtle connections between MSCs and liver lipid metabolism in the PHLF model. We used MSC transplantation to treat PHLF induced by 90% hepatectomy. MSC transplantation could restore the mitochondrial function, promote the beta-oxidation of fatty acid (FA), and reduce the lipid accumulation of hepatocytes. In addition, interleukin 10 (IL-10), a cytokine with immunoregulatory function, had an important role in lipid metabolism. We also found that MSCs transplantation activated the mammalian target of rapamycin (mTOR) pathway. Therefore, we explored the relationship between mitochondrial damage and lipid metabolism abnormality or PHLF. MSCs improved mitochondrial function and corrected abnormal lipid metabolism by affecting the mTOR pathway in the treatment of PHLF. Collectively, MSC transplantation could be used as a potential treatment for PHLF. FAU - Wang, Jing-Lin AU - Wang JL AD - Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China. AD - Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China. AD - Department of Hepatobiliary Surgery, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China. FAU - Ding, Hao-Ran AU - Ding HR AD - Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China. AD - Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China. AD - Department of Hepatobiliary Surgery, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China. FAU - Pan, Chen-Yan AU - Pan CY AD - Department of Hepatobiliary Surgery, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China. FAU - Shi, Xiao-Lei AU - Shi XL AD - Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China. sxl@nju.edu.cn. AD - Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China. sxl@nju.edu.cn. AD - Department of Hepatobiliary Surgery, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China. sxl@nju.edu.cn. FAU - Ren, Hao-Zhen AU - Ren HZ AD - Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China. renhaozhen1984@163.com. AD - Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China. renhaozhen1984@163.com. AD - Department of Hepatobiliary Surgery, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China. renhaozhen1984@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210121 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 SB - IM MH - Animals MH - Female MH - Hepatectomy/*methods MH - Hepatocytes/*metabolism MH - Humans MH - Lipid Metabolism/*physiology MH - Liver Failure/*physiopathology/*therapy MH - Male MH - Mesenchymal Stem Cells/*metabolism MH - Rats MH - Rats, Sprague-Dawley PMC - PMC7820227 COIS- The authors declare that they have no conflict of interest. EDAT- 2021/01/23 06:00 MHDA- 2021/10/05 06:00 PMCR- 2021/01/21 CRDT- 2021/01/22 06:17 PHST- 2020/07/10 00:00 [received] PHST- 2020/12/21 00:00 [accepted] PHST- 2020/12/17 00:00 [revised] PHST- 2021/01/22 06:17 [entrez] PHST- 2021/01/23 06:00 [pubmed] PHST- 2021/10/05 06:00 [medline] PHST- 2021/01/21 00:00 [pmc-release] AID - 10.1038/s41419-020-03374-0 [pii] AID - 3374 [pii] AID - 10.1038/s41419-020-03374-0 [doi] PST - epublish SO - Cell Death Dis. 2021 Jan 21;12(1):111. doi: 10.1038/s41419-020-03374-0.