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Hepatocyte transplantation

Francis D Gratte, Sara Pasic, John K Olynyk, George C T Yeoh, David Tosh, Deirdre R Coombe, Janina E E Tirnitz-Parker
The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium...
March 12, 2018: Scientific Reports
Andrey Elchaninov, Timur Fatkhudinov, Natalia Usman, Irina Arutyunyan, Andrey Makarov, Anastasia Lokhonina, Irina Eremina, Viktor Surovtsev, Dmitry Goldshtein, Galina Bolshakova, Valeria Glinkina, Gennady Sukhikh
AIM: To investigate the influence of the umbilical cord-derived multipotent stromal cells (MSCs) on recovery of the liver after the subtotal resection, that is, removal of 80% of the organ mass, a renowned model of the small-for-size liver remnant syndrome. METHODS: The MSCs were obtained from the intervascular tissue of umbilical cords, dissected from rat fetuses, by the explant culture technique. The vital labeling of MSCs with РКН26 was carried out on the 3rd passage...
February 27, 2018: World Journal of Hepatology
Norman Junge, Qinggong Yuan, Thu Huong Vu, Simon Krooss, Christien Bednarski, Asha Balakrishnan, Toni Cathomen, Michael P Manns, Ulrich Baumann, Amar Deep Sharma, Michael Ott
AIM: To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout ( Fah -/-) mice by homologous-recombination-mediated targeted addition of the Fah gene. METHODS: C57BL/6 Fah∆exon5 mice served as an animal model for human tyrosinaemia type 1 in our study. The vector was created by amplifying human Fah cDNA including the TTR promoter from a lentivirus plasmid as described. The Fah expression cassette was flanked by homologous arms (620 bp and 749 bp long) of the Rosa26 gene locus...
February 27, 2018: World Journal of Hepatology
Gui Pan, Haojie Hao, Jianping Liu
The transplantation of insulin-producing cells (IPCs) or pancreatic progenitor cells is a theoretical therapy for diabetes with insulin insufficiency. Isolated hepatocytes from newborn rats (within 24 h after birth) were progressively induced into IPCs using 5-aza-2'-deoxycytidine, Trichostatin A, retinoic acid, insulin-transferrin-selenium, and nicotinamide. We transplanted Pdx1+ pancreatic progenitors into STZ-induced diabetic mice and found the decreased blood glucose and increased insulin level in comparison with diabetic model...
March 7, 2018: Biochemical and Biophysical Research Communications
Chenyue Ding, Qinyan Zou, Fuxin Wang, Huihua Wu, Rulei Chen, Jinghuan Lv, Mingfa Ling, Jian Sun, Wei Wang, Hong Li, Boxian Huang
BACKGROUND: Although many reports show that various kinds of stem cells have the ability to recover function in premature ovarian aging, few studies have looked at stem cell treatment of natural ovarian aging (NOA). We designed this experimental study to investigate whether human amniotic mesenchymal stem cells (hAMSCs) retain the ability to restore ovarian function, and how hAMSCs work in this process. METHODS: To build the NOA mouse model, the mice were fed for 12-14 months normally with young fertile female mice as the normal control group (3-5 months old)...
March 9, 2018: Stem Cell Research & Therapy
Yusuke Sakai, Makiko Koike, Daisuke Kawahara, Hideko Hasegawa, Tomomi Murai, Kosho Yamanouchi, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Fumihiko Fujita, Tamotsu Kuroki, Susumu Eguchi
Engineered primary hepatocytes, including co-cultured hepatocyte sheets, are an attractive to basic scientific and clinical researchers because they maintain liver-specific functions, have reconstructed cell polarity, and have high transplantation efficiency. However, co-culture conditions regarding engineered primary hepatocytes were suboptimal in promoting these advantages. Here we report that the hepatocyte morphology and liver-specific function levels are controlled by the normal human diploid fibroblast (TIG-118 cell) layer cell density...
March 5, 2018: Journal of Bioscience and Bioengineering
Shuang Zhang, Zhiqiang Zhu, Yufeng Wang, Shi Liu, Chenqiong Zhao, Weijun Guan, Yuhua Zhao
The role of mesenchymal stem cells (MSCs) in cellular therapy is well recognized in this work. MSCs have advantages of high proliferation, clone formation, multi-lineage differentiation and immunosuppression. Furthermore, adipose-resident MSCs (ADSCs) are extensively employed due to its advantages of abundant source, low cost and simple operation. Many researchers have emphasized the role of adipose-resident MSCs in the development of therapies for liver injury, but few attentions were paid on the use of induced functional hepatocytes...
March 7, 2018: Cytotechnology
Francesca Maione, Nicholas Gilbo, Silvia Lazzaro, Peter Friend, Giovanni Camussi, Renato Romagnoli, Jacques Pirenne, Ina Jochmans, Diethard Monbaliu
BACKGROUND: Understanding ischemia reperfusion injury (IRI) is essential to further improve outcomes after liver transplantation (LT). Porcine isolated liver perfusion (ILP) is increasingly used to reproduce LT-associated IRI in a strictly controlled environment. However, whether ILP is a reliable substitute of LT was never validated. METHODS: We systematically reviewed the current experimental set-ups for ILP and parameters of interest reflecting IRI. RESULTS: ILP was never compared to transplantation in animals...
March 5, 2018: Transplantation
Hadrien Tranchart, Martin Gaillard, Papa Saloum Diop, Sylvie Goulinet, Panagiotis Lainas, Ibrahim Dagher
BACKGROUND: Hepatocyte transplantation is a potentially less invasive alternative to liver transplantation for treating inherited metabolic liver diseases. We developed an autotransplantation protocol of ex vivo genetically modified hepatocytes combining lentiviral transduction and transplantation after liver preconditioning by partial portal vein embolization. We investigated the metabolic efficiency of this approach in Watanabe rabbits, animal model of familial hypercholesterolemia...
April 2018: Journal of Surgical Research
Yuan Yan Sin, Laurel L Ballantyne, Christopher R Richmond, Colin D Funk
Progress in gene editing research has been accelerated by utilizing engineered nucleases in combination with induced pluripotent stem cell (iPSC) technology. Here, we report transcription activator-like effector nuclease (TALEN)-mediated reincorporation of Arg1 exons 7 and 8 in iPSCs derived from arginase-1-deficient mice possessing Arg1Δ alleles lacking these terminal exons. The edited cells could be induced to differentiate into hepatocyte-like cells (iHLCs) in vitro and were subsequently used for transplantation into our previously described (Sin et al...
March 2, 2018: Molecular Therapy. Nucleic Acids
Jessica R Salas, Bao Ying Chen, Alicia Wong, Sergio Duarte, Stephanie A K Angarita, Gerald S Lipshutz, Owen N Witte, Peter M Clark
Drug-induced liver failure is a significant indication for a liver transplant, and unexpected liver toxicity is a major reason that otherwise effective therapies are removed from the market. Various methods exist for monitoring liver injury but are often inadequate to predict liver failure. New diagnostic tools are needed. Methods: We evaluate in a preclinical model whether18 F-2-deoxy-2-fluoroarabinose (18 F-DFA), a PET radiotracer that measures the ribose salvage pathway, can be used to monitor acetaminophen-induced liver injury and failure...
March 1, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Xiaosong Li, E Pan, Junke Zhu, Lei Xu, Xuemei Chen, Jingjing Li, Li Liang, Yuan Hu, Jie Xia, Juan Chen, Wannan Chen, Jieli Hu, Kai Wang, Ni Tang, Ailong Huang
Chronic hepatitis B infection remains a serious public health issue worldwide. Hepatitis B virus (HBV) reactivation is commonly reported in patients receiving anticancer therapy, immunosuppressive therapy, or organ and tissue transplantation. However, the precise mechanisms underlying chemotherapeutic agent-related HBV reactivation remain unclear. Here, we report that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) plays a central role in cisplatin-induced HBV transcription and replication...
February 22, 2018: Scientific Reports
Andrew T Trout, Rachel M Sheridan, Suraj D Serai, Stavra A Xanthakos, Weizhe Su, Bin Zhang, Daniel B Wallihan
Purpose To assess the diagnostic performance of magnetic resonance (MR) elastography-derived liver stiffness to detect liver fibrosis in a pediatric and young adult population with a spectrum of liver diseases. Materials and Methods This retrospective study included patients younger than 21 years of age who underwent MR elastography and liver biopsy within 3 months of one another between January 2012 and September 2016 for indications other than liver transplantation or Fontan palliation of congenital heart disease...
February 22, 2018: Radiology
Zhi-Hong Chen, Chao Wang, Fa-Xing Wei, Bin-Bin Xu, Jun Liu, Yong Pu, Shou-Liang Zhang, Peng-Cheng Jiang
BACKGROUND: To discuss the effect and mechanism of adenovirus-mediated OX40Ig gene transfer in inducing long-term survival of liver allografts in rats. METHODS: Orthotopic liver transplantation was performed from Lewis to Brown Norway (BN) rats through the modified two-cuffed technique, and all rats were randomly divided equally into four groups: control, AdEGFP, AdOX40Ig, and FK506. The survival times of the rats were recorded. The rats' liver function, serum cytokines, hepatocyte pathology, OX40Ig protein level, and mixed lymphocyte reaction (MLR) with or without recombinant interleukin-2 (rIL-2) were evaluated...
February 15, 2018: Transplant Immunology
Hailin Zhao, Han Huang, Azeem Alam, Qian Chen, Ka Chuen Suen, Jiang Cui, Qizhe Sun, Rele Ologunde, Wenwen Zhang, Qingquan Lian, Daqing Ma
Clinical evidence indicated a possible link between renal injury and remote liver injury. Herein, we investigated whether extracellular histone mediates remote hepatic damage following renal graft ischemia-reperfusion injury, whilst vascular endothelial growth factor (VEGF) is protective against remote hepatic injury. In vitro, hepatocyte HepG2 cultures were treated with histone. In vivo, the Brown-Norway renal graft was stored in 4°C preserving solution for 24 hours and then transplanted into Lewis rat recipient; blood samples and livers from recipients were harvested 24 hours after surgery...
February 15, 2018: American Journal of Transplantation
S A Townsend, R G Edgar, P R Ellis, D Kantas, P N Newsome, A M Turner
BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is estimated to affect three million people worldwide. It causes liver disease in a proportion of carriers of the PiS and PiZ allele due to the formation and retention of polymers within the endoplasmic reticulum of hepatocytes. The reason for this selective penetrance is not known. Although clinical trials are underway, liver transplantation is the only effective treatment for liver disease due to AATD. AIMS: To report the prevalence and natural history of liver disease among individuals with AATD, and assess the outcomes of liver transplantation through systematic review...
February 15, 2018: Alimentary Pharmacology & Therapeutics
Guizong Chen, Qin Li, Yanping Luo, Tao Liu, Shaolong Zhou, Er Pan, Lixia Peng
Autologous fat particle transplantation has been widely used by surgeons. The present study evaluated the effect of Notoginsenoside R1 (NR1) treatment on rat autologous fat graft, along with the quality and retention rates. Male Sprague‑Dawley rats (n=60) received fat particle auto‑transplantation from the left abdominal cavity into lateral dorsum. A total of 14 days after surgery, NR1 in different doses (50, 100 and 200 mg/kg/day) was injected into rats, following which blood and fat graft samples were harvested at days 7, 14 and 28...
February 13, 2018: Molecular Medicine Reports
Chen Chen, Alejandro Soto-Gutierrez, Pedro M Baptista, Bart Spee
The incidence of liver disease is increasing globally. The only curative therapy for severe end-stage liver disease, liver transplantation, is limited by the shortage of organ donors. In vitro models of liver physiology have been developed and new technologies and approaches are progressing rapidly. Stem cells might be used as a source of liver tissue for development of models, therapies, and tissue-engineering applications. However, we have been unable to generate and maintain stable and mature adult liver cells ex vivo...
February 8, 2018: Gastroenterology
Xiaojiaoyang Li, Runping Liu, Zhiming Huang, Emily C Gurley, Xuan Wang, Juan Wang, Hongliang He, Hu Yang, Guanhua Lai, Luyong Zhang, Jasmohan S Bajaj, Melanie White, William M Pandak, Phillip B Hylemon, Huiping Zhou
Cholestatic liver injury is an important clinical problem with limited understanding of disease pathologies. Exosomes are small extracellular vesicles released by a variety of cells including cholangiocytes. Exosome-mediated cell-cell communication can modulate various cellular functions by transferring a variety of intracellular components to target cells. Our recent studies indicate that the long non-coding RNA H19 is mainly expressed in cholangiocytes and its aberrant expression is associated with significant down-regulation of small heterodimer partner (SHP) in hepatocytes and cholestatic liver injury in multidrug resistance 2 knockout (Mdr2-/- ) mice...
February 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Federica Rigo, Nicola De Stefano, Victor Navarro-Tableros, Ezio David, Giorgia Rizza, Giorgia Catalano, Nicholas Gilbo, Francesca Maione, Federica Gonella, Dorotea Roggio, Silvia Martini, Damiano Patrono, Mauro Salizzoni, Giovanni Camussi, Renato Romagnoli
BACKGROUND: The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). METHODS: We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution...
February 9, 2018: Transplantation
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