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Hepatocyte transplantation

Satoshi Ogiso, Kentaro Yasuchika, Ken Fukumitsu, Takamichi Ishii, Hidenobu Kojima, Yuya Miyauchi, Ryoya Yamaoka, Junji Komori, Hokahiro Katayama, Takayuki Kawai, Elena Yukie Yoshitoshi, Sadahiko Kita, Katsutaro Yasuda, Shinji Uemoto
A whole-organ regeneration approach, using a decellularised xenogeneic liver as a scaffold for the construction of a transplantable liver was recently reported. Deriving suitable scaffolds was the first step towards clinical application; however, effective recellularisation remains to be achieved. This report presents a strategy for the improvement of the recellularisation process, using novel cell-seeding technique and cell source. We evaluated recellularised liver grafts repopulated through the portal vein or the biliary duct with mice adult hepatocytes or E14...
October 21, 2016: Scientific Reports
Laurel L Ballantyne, Yuan Yan Sin, Osama Y Al-Dirbashi, Xinzhi Li, David J Hurlbut, Colin D Funk
Arginase-1 (Arg1) converts arginine to urea and ornithine in the distal step of the urea cycle in liver. We previously generated a tamoxifen-inducible Arg1 deficient mouse model (Arg1-Cre) that disrupts Arg1 expression throughout the whole body and leads to lethality ≈ 2 weeks after gene disruption. Here, we evaluate if liver-selective Arg1 loss is sufficient to recapitulate the phenotype observed in global Arg1 knockout mice, as well as to gauge the effectiveness of gene delivery or hepatocyte transplantation to rescue the phenotype...
December 2016: Molecular Genetics and Metabolism Reports
Nese Karadag, Kerem Tolan, Emine Samdanci, Ayse Selimoglu, Nusret Akpolat, Sezai Yilmaz
OBJECTIVES: Wilson disease is a rare genetic disease with clinical and histopathologic differential diagnostic challenges. In this study, we evaluated the histopathologic findings of explanted livers in Wilson disease, with special emphasis on copper histochemistry. MATERIALS AND METHODS: Our study group was recruited by reviewing archived histopathology reports and the liver transplant clinic patient records retrospectively for patients who had liver transplant for Wilson disease between January 2010 and June 2015, at Turgut Ozal Medical Center...
October 14, 2016: Experimental and Clinical Transplantation
Stacey S Huppert, Kathleen M Campbell
PURPOSE OF REVIEW: Although the liver possesses a unique, innate ability to regenerate through mass compensation, transplantation remains the only therapy when damage outpaces regeneration, or liver metabolic capacity is irreversibly impacted. Recent insight from developmental biology has greatly influenced the advancement of alternative options to transplantation in these settings. RECENT FINDINGS: Factors known to direct liver cell specification, expansion, and differentiation have been used to generate hepatocyte-like cells from stem and somatic cells for developing cell therapies...
October 15, 2016: Current Opinion in Organ Transplantation
Hiroshi Yamazaki
Research over the past 30 years has elucidated the roles of polymorphic human liver cytochrome P450 (P450) enzymes associated with toxicological and/or pharmacological actions. Thalidomide exerts its various pharmacological and toxic actions in primates through multiple mechanisms, including nonspecific modification of many protein networks after bioactivation by autoinduced human P450 enzymes. To overcome species-differences between rodents, currently, nonhuman primates and/or mouse models with transplanted human hepatocytes are used...
October 17, 2016: Chemical Research in Toxicology
Lanjuan Li, Yanhong Zhang, Xiaoping Pan
This method is used to prepare microencapsulation of hepatocytes. The key steps in the protocol are (a) isolation of porcine hepatocytes, followed by (b) production of hepatocytes encapsulation, and (c) evaluation of encapsulations and hepatocytes. This method of collecting porcine hepatocytes was first used in 2003 (Maruyama et al. Cell Transplant 12:593-598, 2003). Cell encapsulation technology was first introduced by Chang (Science 146:524-525, 1964) and later by Lim and Sun in 1980 (Science 210:908-910, 1980)...
2017: Methods in Molecular Biology
Xin-Guang Liu, Yu Liu, Feng Chen
Soluble fibrinogen-like protein 2 (sFGL2) is the soluble form of fibrinogen-like protein 2 belonging to the fibrinogen-related protein superfamily. It is now well characterized that sFGL2 is mainly secreted by regulatory T cell (Treg) populations, and exerts potently immunosuppressive activities. By repressing not only the differentiation and proliferation of T cells but also the maturation of dendritic cells (DCs), sFGL2 acts largely as an immunosuppressant. Moreover, sFGL2 also induces apoptosis of B cells, tubular epithelial cells (TECs), sinusoidal endothelial cells (SECs), and hepatocytes...
October 8, 2016: Oncotarget
Rodrigo Liberal, Charlotte R Grant
Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues...
October 8, 2016: World Journal of Hepatology
Shuyun Liu, Lanlan Zhang, Jingqiu Cheng, Yanrong Lu, Jingping Liu
Inflammatory response is a major cause of grafts dysfunction in islet transplantation. Hepatocyte growth factor (HGF) had shown anti-inflammatory activity in multiple diseases. In this study, we aim to deliver HGF by self-assembling peptide/heparin (SAP/Hep) hybrid gel to protect β-cell from inflammatory injury. The morphological and slow release properties of SAPs were analyzed. Rat INS-1 β-cell line was treated with tumor necrosis factor α in vitro and transplanted into rat kidney capsule in vivo, and the viability, apoptosis, function, and inflammation of β-cells were evaluated...
2016: International Journal of Nanomedicine
Congwen Bian, Yiqi Du, Rui Ding, Jun Huang, Yan Dai, Sujin Bao, Lijuan Zhao, Hefang Shen, Jing Dong, Jianjian Xu, Qiru Xiong, Lili Xu
Biliary complications remain a major source of morbidity in liver transplant patients. Among these complications, nonanastomotic biliary strictures (NAS) are especially common and they are frequently therapy resistant in part because biliary epithelial cells are more sensitive to warm ischemic injury than hepatocytes. It has been a challenge to maintain the physiological function of biliary epithelial cells during liver transplantation. In this work, we have examined the effect of oxygen on proliferation of biliary epithelial cells in the rat livers obtained from donation after circulatory death (DCD)...
2016: American Journal of Translational Research
Tomohide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Masatoshi Ishigami, Yoji Ishizu, Yasuhiro Ogura
Hepatitis C recurrence continues to present a major challenge in liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV)-positive recipients will develop fibrosing cholestatic hepatitis (FCH) after LT. FCH is clinically characterized as marked jaundice with cholestatic hepatic dysfunction and high titers of viremia. Pathologically, FCH manifests as marked hepatocyte swelling, cholestasis, periportal peritrabecular fibrosis and only mild inflammation. This progressive form usually involves acute liver failure, and rapidly results in graft loss...
October 2016: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
Ran-Ran Zhang, Yun-Wen Zheng, Hideki Taniguchi
A novel animal model involving chimeric mice with humanized livers established via human hepatocyte transplantation has been developed. These mice, in which the liver has been repopulated with functional human hepatocytes, could serve as a useful tool for investigating human hepatic cell biology, drug metabolism, and other preclinical applications. One of the key factors required for successful transplantation of human hepatocytes into mice is the elimination of the endogenous hepatocytes to prevent competition with the human cells and provide a suitable space and microenvironment for promoting human donor cell expansion and differentiation...
2016: Journal of Visualized Experiments: JoVE
Heng-Chao Yu, Lu Bai, Zhao-Xu Yang, Hong-Yan Qin, Kai-Shan Tao, Hua Han, Ke-Feng Dou
Ischemia-reperfusion (I/R) is a major reason of hepatocyte injury during liver surgery and transplantation. Myeloid cells including macrophages and neutrophils play important roles in sustained tissue inflammation and damage, but the mechanisms regulating myeloid cells activity have been elusive. In this study, we investigate the role of Notch signaling in myeloid cells during hepatic I/R injury by using a mouse model of myeloid specific conditional knockout of RBP-J. Myeloid-specific RBP-J deletion alleviated hepatic I/R injury...
September 29, 2016: Scientific Reports
Na Shang, Maribel Arteaga, Lennox Chitsike, Fang Wang, Navin Viswakarma, Peter Breslin, Wei Qiu
: Understanding the molecular mechanisms of liver regeneration is essential to improve the survival rate of patients after surgical resection of large amounts of liver tissue. Focal adhesion kinase (FAK) regulates different cellular functions, including cell survival, proliferation and cell migration. The role of FAK in liver regeneration remains unknown. In this study, we found that Fak is activated and induced during liver regeneration after two-thirds partial hepatectomy (PHx). We used mice with liver-specific deletion of Fak and investigated the role of Fak in liver regeneration in 2/3 PHx model (removal of 2/3 of the liver)...
September 28, 2016: Scientific Reports
Silvia Ribback, Verena Sailer, Enrico Böhning, Julia Günther, Jaqueline Merz, Frauke Steinmüller, Kirsten Utpatel, Antonio Cigliano, Kristin Peters, Maria G Pilo, Matthias Evert, Diego F Calvisi, Frank Dombrowski
Activation of the epidermal growth factor receptor (EGFR) signaling pathway promotes the development of hepatocellular adenoma (HCA) and carcinoma (HCC). The selective EGFR inhibitor Gefitinib was found to prevent hepatocarcinogenesis in rat cirrhotic livers. Thus, Gefitinib might reduce progression of pre-neoplastic liver lesions to HCC. In short- and long-term experiments, administration of N-Nitrosomorpholine (NNM) or intrahepatic transplantation of pancreatic islets in diabetic (PTx), thyroid follicles in thyroidectomized (TTx) and ovarian fragments in ovariectomized (OTx) rats was conducted for the induction of foci of altered hepatocytes (FAH)...
2016: International Journal of Molecular Sciences
Keisuke Goda, Tadakazu Takahashi, Akio Kobayashi, Toshiyuki Shoda, Hideyuki Kuno, Shoichiro Sugai
Drug-induced liver injury (DILI) is one of the serious and frequent drug-related adverse events. This adverse event is a main reason for regulatory action pertaining to drugs, including restrictions in clinical indications and withdrawal from clinical trials or the marketplace. Idiosyncratic DILI especially has become a major clinical concern because of its unpredictable nature, frequent hospitalization, need for liver transplantation and high mortality. The estimation of the potential for compounds to induce idiosyncratic DILI is very difficult in non-clinical studies because the precise mechanism of idiosyncratic DILI is still unknown...
2016: Journal of Toxicological Sciences
Tomohide Hori, Yasuhiro Ogura, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Motoshi Kainuma, Hideo Takahashi, Shogo Suzuki, Takashi Ichikawa, Shoko Mizuno, Tadashi Aoyama, Yuki Ishida, Takahiro Hirai, Tomoko Hayashi, Kazuko Hasegawa, Hiromu Takeichi, Atsunobu Ota, Yasuhiro Kodera, Hiroyuki Sugimoto, Taku Iida, Shintaro Yagi, Kentaro Taniguchi, Shinji Uemoto
Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation (LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT...
September 8, 2016: World Journal of Hepatology
Daniëlle G Leuning, Marlies E J Reinders, Joan Li, Anna J Peired, Ellen Lievers, Hetty C de Boer, Willem E Fibbe, Paola Romagnani, Cees van Kooten, Melissa H Little, Marten A Engelse, Ton J Rabelink
: : Mesenchymal stromal cells (MSCs) are immunomodulatory and tissue homeostatic cells that have shown beneficial effects in kidney diseases and transplantation. Perivascular stromal cells (PSCs) identified within several different organs share characteristics of bone marrow-derived MSCs (BM-MSCs). These PSCs may also possess tissue-specific properties and play a role in local tissue homeostasis. We hypothesized that human kidney-derived PSCs (hkPSCs) would elicit improved kidney repair in comparison with BM-MSCs...
September 20, 2016: Stem Cells Translational Medicine
Jing Shan, David J Logan, David E Root, Anne E Carpenter, Sangeeta N Bhatia
Liver disease is a leading cause of morbidity worldwide and treatment options are limited, with organ transplantation being the only form of definitive management. Cell-based therapies have long held promise as alternatives to whole-organ transplantation but have been hindered by the rapid loss of liver-specific functions over a period of days in cultured hepatocytes. Hypothesis-driven studies have identified a handful of factors that modulate hepatocyte functions in vitro, but our understanding of the mechanisms involved remains incomplete...
October 2016: Journal of Biomolecular Screening
Clara T Nicolas, Raymond D Hickey, Harvey S Chen, Shennen A Mao, Manuela Lopera Higuita, Yujia Wang, Scott L Nyberg
Donor organ shortage is the main limitation to liver transplantation as a treatment for end-stage liver disease and acute liver failure. Liver regenerative medicine may in the future offer an alternative form of therapy for these diseases, be it through cell transplantation, bioartificial liver (BAL) devices, or bioengineered whole organ liver transplantation. All three strategies have shown promising results in the past decade. However, before they are incorporated into widespread clinical practice, the ideal cell type for each treatment modality must be found, and an adequate amount of metabolically active, functional cells must be able to be produced...
September 19, 2016: Stem Cells
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