PMID- 24005538 OWN - NLM STAT- MEDLINE DCOM- 20140907 LR - 20211021 IS - 1689-1392 (Electronic) IS - 1425-8153 (Print) IS - 1425-8153 (Linking) VI - 18 IP - 4 DP - 2013 Dec TI - In vitro and in vivo characteristics of hepatic oval cells modified with human hepatocyte growth factor. PG - 507-21 LID - 10.2478/s11658-013-0104-1 [doi] AB - Hepatocyte growth factor (HGF) is a multifunctional growth factor that controls cell scattering. It has been suggested that it regulates the proliferation of hepatic oval cells (HOCs). Using a HOC line that stably expresses the human HGF gene (hHGF), we investigated the in vitro proliferation and differentiation characteristics of hHGF-modified HOCs and explored their potential capacity for intrahepatic transplantation. A modified 2-acetylaminofluorene and partial hepatectomy (2-AAF/PH) model was established to activate the proliferation of oval cells in the rat liver. HOCs were transfected with the pBLAST2-hHGF plasmid and hHGF-carrying HOCs were selected based on blasticidin resistance. The level of hHGF secretion was determined via ELISA. Cell proliferation was determined using the MTT assay. Differentiation was induced by growth factor withdrawal. A two-cuff technique was used for orthotopic liver transplantation, and HOCs or hHGF-modified HOCs were transplanted into the recipients. The levels of biochemical indicators of liver function were measured after transplantation. An HOC line stably expressing hHGF was established. The transfected line showed greater hHGF secretion than normal HOCs. The hHGF gene promoted the proliferation capability of HOCs by reducing the peak time in vitro. The hHGF-modified HOCs differentiated into hepatocytes and bile duct epithelial cells upon growth factor withdrawal in vitro. In addition, hHGF-modified HOC transplantation significantly prolonged the median survival time (MST) and improved the liver function of recipients compared to HOC transplant recipients and nontransplanted controls. Our results indicate that hHGF-modified HOCs may have valuable properties for therapeutic liver regeneration after orthotopic liver transplantation. FAU - Li, Zhu AU - Li Z AD - Department of Hepatobiliary Surgery, Liaocheng People's Hospital, No. 67 Dongchang West Road, Liaocheng, 252000, Shandong, China, lllllzhu@126.com. FAU - Chen, Juan AU - Chen J FAU - Li, Li AU - Li L FAU - Ran, Jiang-Hua AU - Ran JH FAU - Li, Xue-Hua AU - Li XH FAU - Liu, Zhi-Heng AU - Liu ZH FAU - Liu, Gui-Jie AU - Liu GJ FAU - Gao, Yan-Chao AU - Gao YC FAU - Zhang, Xue-Li AU - Zhang XL FAU - Sun, Hiu-Dong AU - Sun HD LA - eng PT - Journal Article DEP - 20130904 PL - England TA - Cell Mol Biol Lett JT - Cellular & molecular biology letters JID - 9607427 RN - 0 (HGF protein, human) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Animals MH - Cell Differentiation MH - Cell Engineering/methods MH - Cell Proliferation MH - Cells, Cultured MH - Female MH - Hepatocyte Growth Factor/*genetics/metabolism MH - Hepatocytes/cytology/*metabolism/*transplantation MH - Humans MH - Liver/cytology/*injuries/*physiology/surgery MH - *Liver Regeneration MH - Male MH - Plasmids/administration & dosage/genetics MH - Rats MH - Rats, Inbred Lew MH - Transfection PMC - PMC6275751 EDAT- 2013/09/06 06:00 MHDA- 2014/09/10 06:00 PMCR- 2013/09/04 CRDT- 2013/09/06 06:00 PHST- 2012/11/06 00:00 [received] PHST- 2013/08/29 00:00 [accepted] PHST- 2013/09/06 06:00 [entrez] PHST- 2013/09/06 06:00 [pubmed] PHST- 2014/09/10 06:00 [medline] PHST- 2013/09/04 00:00 [pmc-release] AID - 104 [pii] AID - 10.2478/s11658-013-0104-1 [doi] PST - ppublish SO - Cell Mol Biol Lett. 2013 Dec;18(4):507-21. doi: 10.2478/s11658-013-0104-1. Epub 2013 Sep 4.