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Hepatocyte transplantation

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https://www.readbyqxmd.com/read/29145424/levosimendan-protects-human-hepatocytes-from-ischemia-reperfusion-injury
#1
Stefanie N Brunner, Nicolai V Bogert, Andreas A Schnitzbauer, Eva Juengel, Anton Moritz, Isabella Werner, Angela Kornberger, Andres Beiras-Fernandez
BACKGROUND: Ischemia-reperfusion injury (IRI) is a major challenge in liver transplantation. The mitochondrial pathway plays a pivotal role in hepatic IRI. Levosimendan, a calcium channel sensitizer, was shown to attenuate apoptosis after IRI in animal livers. The aim of this study was to investigate the effect of levosimendan on apoptosis in human hepatocytes. METHODS: Primary human hepatocytes were either exposed to hypoxia or cultured under normoxic conditions...
2017: PloS One
https://www.readbyqxmd.com/read/29138835/mesenchymal-stem-cells-overexpressing-adrenomedullin-improve-heart-function-through-antifibrotic-action-in-rats-experiencing-heart-failure
#2
Li Li Li, Cheng Peng, Meiling Zhang, Yumei Liu, Hefei Li, Huibo Chen, Yu Sun, Chunjun Zhu, Yao Zhang
Previous studies of the authors have indicated that the transplantation of mesenchymal stem cells (MSCs) can attenuate cardiac fibrosis through the secretion of antifibrotic factors, such as adrenomedullin (ADM). Therefore, the authors addressed the hypothesis that ADM overexpression could enhance the antifibrotic effect of MSCs transplantation in a rat model of heart failure. The results of the present study demonstrated that, compared with the group that received the GFP‑MSCs, the transplantation of ADM‑MSCs significantly improved heart function and decreased the percentage of fibrotic area and the expression of matrix metalloproteinase 2...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29130076/crispr-correction-of-a-homozygous-low-density-lipoprotein-receptor-mutation-in-familial-hypercholesterolemia-induced-pluripotent-stem-cells
#3
Linda Omer, Elizabeth A Hudson, Shirong Zheng, James B Hoying, Yuan Shan, Nolan L Boyd
Familial hypercholesterolemia (FH) is a hereditary disease primarily due to mutations in the low-density lipoprotein receptor (LDLR) that lead to elevated cholesterol and premature development of cardiovascular disease. Homozygous FH patients (HoFH) with two dysfunctional LDLR alleles are not as successfully treated with standard hypercholesterol therapies, and more aggressive therapeutic approaches to control cholesterol levels must be considered. Liver transplant can resolve HoFH, and hepatocyte transplantation has shown promising results in animals and humans...
November 2017: Hepatol Commun
https://www.readbyqxmd.com/read/29127685/the-first-case-of-ischemia-free-organ-transplantation-in-humans-a-proof-of-concept
#4
Xiaoshun He, Zhiyong Guo, Qiang Zhao, Weiqiang Ju, Dongping Wang, Linwei Wu, Lu Yang, Fei Ji, Yunhua Tang, Zhiheng Zhang, Shanzhou Huang, Linhe Wang, Zebin Zhu, Kunpeng Liu, Yanling Zhu, Yifang Gao, Wei Xiong, Ming Han, Bing Liao, Maogen Chen, Yi Ma, Xiaofeng Zhu, Wenqi Huang, Changjie Cai, Xiangdong Guan, Xian Chang Li, Jiefu Huang
Ischemia and reperfusion injury (IRI) is an inevitable event in conventional organ transplant procedure and is associated with significant mortality and morbidity post-transplantation. We hypothesize that IRI is avoidable if the blood supply for the organ is not stopped, thus resulting in optimal transplant outcomes. Here we described the first case of a novel procedure called ischemia-free organ transplantation (IFOT) for patients with end-stage liver disease. The liver graft with severe macrovesicular steatosis was donated from a 25-year-old man...
November 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29121675/astaxanthin-prevents-ischemia-reperfusion-injury-of-the-steatotic-liver-in-mice
#5
Shaowei Li, Terumi Takahara, Masayuki Fujino, Yasuyuki Fukuhara, Toshiro Sugiyama, Xiao-Kang Li, Shiro Takahara
Steatosis has a low tolerance against ischemia-reperfusion injury (IRI). To prevent IRI in the steatotic liver, we attempted to elucidate the protective effect of astaxanthin (ASTX) in the steatotic liver model by giving mice a methionine and choline-deficient high fat (MCDHF) diet. Levels of lipid peroxidation and apoptosis, the expression of inflammatory cytokines and heme oxygenase (HO)-1, in the liver were assessed. Reactive oxygen species (ROS), inflammatory cytokines, apoptosis-related proteins and members of the signaling pathway were also examined in isolated Kupffer cells and/or hepatocytes from the steatotic liver...
2017: PloS One
https://www.readbyqxmd.com/read/29109103/hepatocyte-nuclear-factor-1a-deficiency-causes-hemolytic-anemia-in-mice-by-altering-erythrocyte-sphingolipid-homeostasis
#6
Karin von Wnuck Lipinski, Sarah Weske, Petra Keul, Susann Peters, Hideo A Baba, Gerd Heusch, Markus H Gräler, Bodo Levkau
The Hepatocyte Nuclear Factor (HNF) family regulates complex networks of metabolism and organ development. Human mutations in its prototypical member HNF1A cause maturity-onset of diabetes of the young (MODY) type 3. In this study, we identified an important role for HNF1A in the preservation of erythrocyte membrane integrity, calcium homeostasis and osmotic resistance through a yet unrecognized link of HNF1A to sphingolipid homeostasis. HNF1A(-/-) mice displayed microcytic hypochromic anemia with reticulocytosis that was partially compensated by avid extramedullary erythropoiesis at all erythroid stages in the spleen thereby excluding erythroid differentiation defects...
November 6, 2017: Blood
https://www.readbyqxmd.com/read/29108215/-research-advances-in-the-role-of-mesenchymal-stem-cells-and-their-exosomes-in-treatment-of-liver-diseases
#7
W H Niu, J J Zhang, Z Y Zhu
At present, liver transplantation remains the most effective treatment for acute liver failure and advanced cirrhosis, but its use and promotion are limited by insufficient organ donors, financial consideration, and requirements for lifelong immunosuppression. In recent years, stem cell transplantation has been recommended as an effective substitutive therapy for liver disease. Mesenchymal stem cells, also known as pluripotent interstitial stromal cells, are self-renewing cells that can be found in almost all postnatal organs and tissues, including the liver...
October 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29107021/historical-perspectives-and-advances-in-the-mesenchymal-stem-cell-research-for-the-treatment-of-liver-diseases
#8
REVIEW
Chien-Wei Lee, Yu-Fan Chen, Hao-Hsiang Wu, Oscar K Lee
Liver transplantation is the only effective therapy for patients with decompensated cirrhosis and fulminant liver failure. However, due to a shortage of donor livers and complications associated with immune suppression, there is an urgent need for new therapeutic strategies for patients with end-stage liver diseases. Given their unique function in self-renewal and differentiation potential, stem cells might be used to regenerate damaged liver tissue. Recent studies have shown that stem cell-based therapies can improve liver function in a mouse model of hepatic failure...
October 26, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29101679/simple-and-quick-method-to-obtain-a-decellularized-functional-liver-bioscaffold
#9
Matteo Ghiringhelli, Alessandro Zenobi, Stefano Brizzola, Fulvio Gandolfi, Valentino Bontempo, Sandro Rossi, Tiziana A L Brevini, Fabio Acocella
The development of new approaches for organ transplantation has become crucial in the last years. In particular, organ engineering, involving the preparation of acellular matrices that provide a natural habitat for reseeding with an appropriate population of cells, is an attractive although technically demanding approach. We here describe a method that allows for the derivation of functional in vitro hepatic organoids and that does not require a previous selection of all the parenchymal hepatocytes and non-parenchymal cells, namely, Kupffer cells, liver endothelial cells, and hepatic stellate cells...
November 4, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29097870/adipose-derived-stromal-cells-resemble-bone-marrow-stromal-cells-in-hepatocyte-differentiation-potential-in-vitro-and-in-vivo
#10
Li-Juan Xu, Shu-Fang Wang, De-Qing Wang, Lian-Jun Ma, Zheng Chen, Qian-Qian Chen, Jun Wang, Li Yan
AIM: To investigate whether mesenchymal stem cells (MSCs) from adipose-derived stromal cells (ADSCs) and bone marrow stromal cells (BMSCs) have similar hepatic differentiation potential. METHODS: Mouse ADSCs and BMSCs were isolated and cultured. Their morphological and phenotypic characteristics, as well as their multiple differentiation capacity were compared. A new culture system was established to induce ADSCs and BMSCs into functional hepatocytes. Reverse transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to identify the induced hepatocyte-like cells...
October 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29096561/in-silico-modeling-to-optimize-interpretation-of-liver-safety-biomarkers-in-clinical-trials
#11
Rachel J Church, Paul B Watkins
Current strategies to delineate the risk of serious drug-induced liver injury associated with drugs rely on assessment of serum biomarkers that have been utilized for many decades. In particular, serum alanine aminotransferase and total bilirubin levels are typically used to assess hepatic integrity and function, respectively. Parallel measurement of these biomarkers is utilized to identify patients with drug-induced hepatocellular jaundice ("Hy's Law" cases) which carries at least a 10% risk of death or liver transplant...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29091890/the-effect-of-clinically-relevant-doses-of-immunosuppressive-drugs-on-human-mesenchymal-stem-cells
#12
Eliska Javorkova, Julie Vackova, Michaela Hajkova, Barbora Hermankova, Alena Zajicova, Vladimir Holan, Magdalena Krulova
Immunosuppressive drugs are used to suppress graft rejection after transplantation and for the treatment of various diseases. The main limitations of their use in clinical settings are severe side effects, therefore alternative approaches are desirable. In this respect, mesenchymal stem cells (MSCs) possess a regenerative and immunomodulatory capacity that has generated considerable interest for their use in cell-based therapy. Currently, MSCs are tested in many clinical trials, including the treatment of diseases which require simultaneous immunosuppressive treatment...
October 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29082074/optical-imaging-for-the-assessment-of-hepatocyte-metabolic-state-in-ischemia-and-reperfusion-injuries
#13
Mette F la Cour, Shima Mehrvar, Joohyun Kim, Alicia Martin, Michael A Zimmerman, Johnny C Hong, Mahsa Ranji
Deterioration in mitochondrial function leads to hepatic ischemia and reperfusion injury (IRI) in liver surgery and transplantation. 3D optical cryoimaging was used to measure the levels of mitochondrial coenzymes NADH and FAD, and their redox ratio (NADH/FAD) gave a quantitative marker for hepatocyte oxidative stress during IRI. Using a rat model, five groups were compared: control, ischemia for 60 or 90 minutes (Isc60, Isc90), ischemia for 60 or 90 minutes followed by reperfusion of 24 hours (IRI60, IRI90)...
October 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/29078082/evaluating-the-regenerative-potential-and-functionality-of-human-liver-cells-in-mice
#14
REVIEW
Antson Kiat Yee Tan, Kyle M Loh, Lay Teng Ang
Liver diseases afflict millions of patients worldwide. Currently, the only long-term treatment for liver failure is the transplantation of a new liver. However, intravenously transplanting a suspension of human hepatocytes might be a less-invasive approach to partially reconstitute lost liver functions in human patients as evinced by promising outcomes in clinical trials. The purpose of this essay is to emphasize outstanding questions that continue to surround hepatocyte transplantation. While adult primary human hepatocytes are the gold standard for transplantation, hepatocytes are heterogeneous...
September 18, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29066412/schisandrol-b-promotes-liver-regeneration-after-partial-hepatectomy-in-mice
#15
Xi Li, Jiahong Sun, Xiaomei Fan, Lihuan Guan, Dongshun Li, Yawen Zhou, Xuezhen Zeng, Yixin Chen, Huizhen Zhang, Leqian Xu, Fulin Jiang, Min Huang, Huichang Bi
Liver regeneration is a vital process of recovery after liver damage, which is a promising clinical strategy after partial hepatectomy (PHx). Schisandrol B (SolB), one of the bioactive ingredients from Schisandra sphenanthera, displays significant hepato-protection effects against drug-induced liver injure in mice. However, the effect of SolB on liver regeneration after PHx remains unclear. Here, we showed that SolB treatment promoted liver mass restoration and increased the number of proliferative hepatocytes following PHx...
October 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29059701/interferon-regulatory-factor-1-rab27a-regulated-extracellular-vesicles-promote-liver-ischemia-reperfusion-injury
#16
Mu-Qing Yang, Qiang Du, Julie Goswami, Patrick R Varley, Bin Chen, Rong-Hua Wang, Adrian E Morelli, Donna B Stolz, Timothy R Billiar, Jiyu Li, David A Geller
The role and regulators of extracellular vesicles (EV) secretion in hepatic ischemia/reperfusion (IR) injury have not been defined. Rab27a is a GTPase known to control EVs release. Interferon regulatory factor 1 (IRF-1) is a transcription factor that plays an important role in liver IR and regulates certain GTPases. However, the relationships among IRF-1, Rab27a, and EVs secretion are largely unknown. Here, we show induction of IRF-1 and Rab27a both in vitro in hypoxic hepatocytes and in vivo in warm IR and orthotopic liver transplantation livers...
October 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29052747/angiosomal-radiopathologic-analysis-of-transarterial-radioembolization%C3%A2-for-the-treatment-of-hepatocellular-carcinoma
#17
Altan F Ahmed, Naziya Samreen, Joseph R Grajo, Ivan Zendejas, Chris L Sistrom, Amy Collinsworth, Ashwini Esnakula, Jehan L Shah, Roniel Cabrera, Brian S Geller, Beau B Toskich
PURPOSE: To assess the radiopathologic correlation following Yttrium-90 transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) using variable radiodosimetry to identify imaging surrogates of histologic response. METHODS: Twelve patients with HCC underwent ablative (≥ 190 Gy) and/or non-ablative (< 190 Gy) TARE delivered in a segmental, lobar, or combined fashion as a surgical neoadjuvant or bridge to transplantation. Both targeted tumor and treatment angiosome were analyzed before and after TARE utilizing hepatocyte-specific contrast-enhanced MRI or contrast-enhanced CT...
October 20, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/29052367/decellularized-caprine-liver-extracellular-matrix-as-a-2d-substrate-coating-and-3d-hydrogel-platform-for-vascularized-liver-tissue-engineering
#18
Tarun Agarwal, Rajan Narayan, Somnath Maji, Sudip Kumar Ghosh, Tapas Kumar Maiti
Development of a vascularized liver tissue construct is a need of an hour to circumvent the current demand of liver transplantation in healthcare sector. An appropriate matrix must support liver cell viability, functionality, and development of microvasculature. With this perspective, here, we report the use of decellularized Caprine liver ECM (CLECM) derived hydrogel for tissue engineering applications. First, CLECM was used as a substrate coating material for 2D hepatocyte culture. HepG2 cells cultured on CLECM coated surface showed higher albumin, urea, glycogen and GAGs synthesis in comparison to collagen coated surface (taken as control for the study)...
October 19, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29042291/micrornas-as-biomarkers-for-liver-injury-current-knowledge-challenges-and-future-prospects
#19
REVIEW
Haixia Lin, Laura E Ewing, Igor Koturbash, Bill J Gurley, Isabelle R Miousse
MicroRNAs (miRNAs) are short regulatory RNAs that are involved in various biological processes that regulate gene expression posttranscriptionally. Changes in miRNA expression can be detected in many physiological and pathological events, such as liver injury. Drug induced liver injury is a life threatening condition that frequently requires organ transplantation. Hepatotoxicity is also one of the major causes of drug failure in clinical trials and of drug withdrawal from the market. The profiling of miRNA expression shows great promise in monitoring liver injury, in the prediction of outcome in patients, and in the identification of liver-reactive compounds in toxicological assessment...
October 16, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29024427/combined-liver-kidney-perfusion-enhances-protective-effects-of-normothermic-perfusion-on-livers-grafts-from-donation-after-cardiac-death
#20
Xiaoshun He, Fei Ji, Zhiheng Zhang, Yunhua Tang, Lu Yang, Shanzhou Huang, Wenwen Li, Qiao Su, Wei Xiong, Zebin Zhu, Linhe Wang, Lei Lv, Jiyou Yao, Linan Zhang, Longjuan Zhang, Zhiyong Guo
It has been showed that combined liver-kidney normothermic machine perfusion (NMP) is able to better maintain the circuit's biochemical milieu. Nevertheless, whether the combined perfusion is superior to liver perfusion alone in protecting livers from donation after cardiac death (DCD) is unclear. We aimed to test the hypothesis and explored the mechanisms. Livers from 15 DCD pig donors were subjected to either static cold storage group (Group A), liver alone NMP group (Group B), or combined liver-kidney NMP group (Group C)...
October 10, 2017: Liver Transplantation
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