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liver repopulation

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https://www.readbyqxmd.com/read/28088007/impairment-of-host-liver-repopulation-by-transplanted-hepatocytes-in-aged-rats-and-the-release-by-short-term-growth-hormone-treatment
#1
Peggy Stock, Maximilian Bielohuby, Martin S Staege, Mei-Ju Hsu, Martin Bidlingmaier, Bruno Christ
Hepatocyte transplantation is an alternative to whole liver transplantation. Yet, efficient liver repopulation by transplanted hepatocytes is low in livers of old animals. This restraint might be because of the poor proliferative capacity of aged donor hepatocytes or the regenerative impairment of the recipient livers. The age-dependent liver repopulation by transplanted wild-type hepatocytes was investigated in juvenile and senescent rats deficient in dipeptidyl-peptidase IV. Repopulation was quantified by flow cytometry and histochemical estimation of dipeptidyl-peptidase IV enzyme activity of donor cells in the negative host liver...
January 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28053091/fumarylacetoacetate-hydrolase-knockout-rabbit-model-for-hereditary-tyrosinemia-type-1
#2
Li Li, Quanjun Zhang, Huaqiang Yang, Qingjian Zou, Chengdan Lai, Fei Jiang, Ping Zhao, Zhiwei Luo, Jiayin Yang, Qian Chen, Yan Wang, Philip N Newsome, Jon Frampton, Patrick H Maxwell, Wenjuan Li, Shuhan Chen, Dongye Wang, Tak-Shing Siu, Sidney Tam, Hung-Fat Tse, Baoming Qin, Xichen Bao, Miguel A Esteban, Liangxue Lai
Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedion (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone...
January 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28029279/recellularization-via-the-bile-duct-supports-functional-allogenic-and-xenogenic-cell-growth-on-a-decellularized-rat-liver-scaffold
#3
Wessam Hassanein, Mehmet C Uluer, John Langford, Jhade D Woodall, Arielle Cimeno, Urmil Dhru, Avraham Werdesheim, Joshua Harrison, Carlos Rivera-Pratt, Stephen Klepfer, Ali Khalifeh, Bryan Buckingham, Philip S Brazio, Dawn Parsell, Charlie Klassen, Cinthia Drachenberg, Rolf N Barth, John C LaMattina
Recent years have seen a proliferation of methods leading to successful organ decellularization. In this experiment we examine the feasibility of a decellularized liver construct to support growth of functional multilineage cells. Bio-chamber systems were used to perfuse adult rat livers with 0.1% SDS for 24 hours yielding decellularized liver scaffolds. Initially, we recellularized liver scaffolds using a human tumor cell line (HepG2, introduced via the bile duct). Subsequent studies were performed using either human tumor cells co-cultured with human umbilical vein endothelial cells (HUVECs, introduced via the portal vein) or rat neonatal cell slurry (introduced via the bile duct)...
December 28, 2016: Organogenesis
https://www.readbyqxmd.com/read/27975325/studying-hbv-infection-and-therapy-in-immune-deficient-nod-rag1-il2rgammac-null-nrg-fumarylacetoacetate-hydrolase-fah-knockout-mice-transplanted-with-human-hepatocytes
#4
Feng Li, Kouki Nio, Fumihiko Yasui, Christopher M Murphy, Lishan Su
Chimeric mouse models with a humanized liver provide a unique tool to study hepatic virus diseases, including viral infection, viral pathogenesis, and antiviral therapy. Here we describe a detailed protocol for studying hepatitis B infection in NRG-derived fumarylacetoacetate hydrolase (Fah) knockout mice repopulated with human hepatocytes. The procedures include (1) maintenance and genotyping of the homozygous NRG-fah/fah mutant mice (NRG/F), (2) intrasplenic injection of human hepatocytes, (3) NTBC drug reduction cycling to improve human hepatocyte repopulation, (4) human albumin detection, and (5) HBV infection and detection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27958775/distinct-molecular-signature-of-murine-fetal-liver-and-adult-hematopoietic-stem-cells-identifies-novel-regulators-of-hematopoietic-stem-cell-function
#5
Javed Karim Manesia, Monica Franch, Daniel Tabas-Madrid, Ruben Nogales-Cadenas, Thomas Vanwelden, Elisa Van Den Bosch, Zhuofei Xu, Alberto Pascual-Montano, Satish Khurana, Catherine Verfaillie
During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, while HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA-sequencing based gene expression analysis on FL HSCs from 14.5 day mouse embryo (E14.5) in comparison to the ABM HSCs...
December 13, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27957815/evolution-of-graft-morphology-and-function-after-recellularization-of-decellularized-rat-livers
#6
Antje Butter, Khalid Aliyev, Karl-Herbert Hillebrandt, Nathanael Raschzok, Martin Kluge, Nicolai Seiffert, Peter Tang, Hendrik Napierala, Muhammad Imtiaz Ashraf, Anja Reutzel-Selke, Andreas Andreou, Johann Pratschke, Igor Maximilian Sauer, Benjamin Struecker
Decellularization of livers is a well-established procedure. Data on different reseeding techniques or the functional evolution and re-organization processes of repopulated grafts remains limited. We established a proprietary, customized bioreactor to repopulate decellularized rat livers (n = 21) with primary rat hepatocytes (150 x 10(6) cells) via the hepatic artery and to subsequently evaluate graft morphology and function during seven days of ex vivo perfusion. Grafts were analyzed at 1 h, 6 h, 12 h, 24 h, 3d, 5d and 7d after recellularization (all n = 3) by immuno-histologic evaluation, hepatocyte-related enzyme (AST, ALT, LDH) and albumin measurement in the perfusate...
December 13, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27915139/impairment-of-fetal-hematopoietic-stem-cell-function-in-the-absence-of-fancd2
#7
Sakiko Suzuki, Ronny R Racine, Nathan A Manalo, Sharon B Cantor, Glen D Raffel
Fanconi anemia (FA) results from mutations in the genes necessary for DNA damage repair and often leads to progressive bone marrow failure. Although the exhaustion of the bone marrow leads to cytopenias in FA patients as they age, evidence from human FA and mouse model fetal livers suggests that hematopoietic defects originate in utero, which may lead to deficient seeding of the bone marrow. To address this possibility, we examined the consequences of loss of Fancd2, a central component of the FA pathway. Examination of embryonic day 14...
December 1, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27882948/the-non-canonical-wnt-receptor-ryk-regulates-hematopoietic-stem-cell-repopulation-in-part-by-controlling-proliferation-and-apoptosis
#8
Farbod Famili, Laura Garcia Perez, Brigitta Ae Naber, Jasprina N Noordermeer, Lee G Fradkin, Frank Jt Staal
The development of blood and immune cells requires strict control by various signaling pathways in order to regulate self-renewal, differentiation and apoptosis in stem and progenitor cells. Recent evidence indicates critical roles for the canonical and non-canonical Wnt pathways in hematopoiesis. The non-canonical Wnt pathway is important for establishment of cell polarity and cell migration and regulates apoptosis in the thymus. We here investigate the role of the non-canonical Wnt receptor Ryk in hematopoiesis and lymphoid development...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27862079/discarded-livers-find-a-new-life-engineered-liver-grafts-using-hepatocytes-recovered-from-marginal-livers
#9
Basak E Uygun, Maria-Louisa Izamis, Maria Jaramillo, Yibin Chen, Gavrielle Price, Sinan Ozer, Martin L Yarmush
Treatment for end-stage liver failure is restricted by the critical shortage of donor organs; about 4000 people die in the USA while waiting for a transplantable organ. This situation has been a major driving force behind the rise of tissue engineering to build artificial tissues/organs. Recent advancements in creating transplantable liver grafts using decellularized liver scaffolds bring the field closer to clinical translation. However, a source of readily available and highly functional adult hepatocytes in adequate numbers for regenerative liver therapies still remains unclear...
November 8, 2016: Artificial Organs
https://www.readbyqxmd.com/read/27857132/mfsd2a-hepatocytes-repopulate-the-liver-during-injury-and-regeneration
#10
Wenjuan Pu, Hui Zhang, Xiuzhen Huang, Xueying Tian, Lingjuan He, Yue Wang, Libo Zhang, Qiaozhen Liu, Yan Li, Yi Li, Huan Zhao, Kuo Liu, Jie Lu, Yingqun Zhou, Pengyu Huang, Yu Nie, Yan Yan, Lijian Hui, Kathy O Lui, Bin Zhou
Hepatocytes are functionally heterogeneous and are divided into two distinct populations based on their metabolic zonation: the periportal and pericentral hepatocytes. During liver injury and regeneration, the cellular dynamics of these two distinct populations remain largely elusive. Here we show that major facilitator super family domain containing 2a (Mfsd2a), previously known to maintain blood-brain barrier function, is a periportal zonation marker. By genetic lineage tracing of Mfsd2a(+) periportal hepatocytes, we show that Mfsd2a(+) population decreases during liver homeostasis...
November 18, 2016: Nature Communications
https://www.readbyqxmd.com/read/27830554/minimally-invasive-liver-preconditioning-for-hepatocyte-transplantation-in-rats
#11
Martin Gaillard, Ibrahim Dagher
In the context of cell transplantation in the liver parenchyma, preconditioning is essential to enhance cell engraftment and liver repopulation. The authors have developed a minimally invasive technique of temporary portal embolization using an absorbable material, called reversible portal vein embolization. We hereby describe the method for isolating hepatocytes from a donor rat before transplanting hepatocytes after reversible portal vein embolization in the recipient.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830548/fetal-liver-stem-progenitor-cell-transplantation-a-model-to-study-tissue-mass-replacement-and-cell-based-therapies
#12
Mladen I Yovchev, Michael Oertel
Liver transplantation is the only therapeutic treatment for patients with end-stage liver diseases. However, donor organ scarcity is the major limitation, and therefore, alternative strategies are urgently needed. The ultimate goal for successful cell-based therapies is the ability of transplanted cells to efficiently engraft and reconstitute injured liver mass. To evaluate the repopulation capacity of transplanted cells, it is essential to identify their specific characteristics, as well as to study the mechanism(s) Through which transplanted donor cells replace tissue mass in hepatic microenvironments, using well-established cell transplantation models...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830547/propagation-of-human-hepatocytes-in-upa-scid-mice-producing-chimeric-mice-with-humanized-liver
#13
Hiroki Ohshita, Chise Tateno
Primary or cryopreserved human hepatocytes (h-heps) have been used as the gold standard for in vitro metabolism and hepatotoxicity studies; however, the supply of h-heps is limited and they cannot grow in vitro. We achieved approximately 1000-fold propagation of h-heps in the liver of albumin promoter/enhancer-driven urokinase-type plasminogen activator transgenic/severe combined immunodeficiency disease (uPA/SCID) mice with genetically induced liver disease and immunodeficiency. When h-heps are transplanted into the uPA/SCID mouse liver via the spleen, the h-heps engraft in the mouse liver, resulting in its repopulation with h-heps...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830544/late-gestation-fetal-hepatocytes-for-liver-repopulation-in-the-rat
#14
Jennifer A Sanders
Cellular transplantation represents an alternative to liver transplantation for the treatment of end-stage liver disease and liver-based inborn errors of metabolism. In order for cellular transplantation to be successful, an optimal source of cells for transplantation needs to be identified and the molecular mechanisms regulating their engraftment, proliferation, and functional differentiation elucidated. Here we describe a detailed protocol for the isolation, selection, and transplantation into an injured adult rat liver of a defined population of late gestation fetal rat hepatocytes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27805597/study-of-viral-vectors-in-a-three-dimensional-liver-model-repopulated-with-the-human-hepatocellular-carcinoma-cell-line-hepg2
#15
Thomas Hiller, Viola Röhrs, Eva-Maria Dehne, Anke Wagner, Henry Fechner, Roland Lauster, Jens Kurreck
This protocol describes the generation of a three-dimensional (3D) ex vivo liver model and its application to the study and development of viral vector systems. The model is obtained by repopulating the extracellular matrix of a decellularized rat liver with a human hepatocyte cell line. The model permits studies in a vascularized 3D cell system, replacing potentially harmful experiments with living animals. Another advantage is the humanized nature of the model, which is closer to human physiology than animal models...
October 24, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27789682/disrupted-murine-gut-to-human-liver-signaling-alters-bile-acid-homeostasis-in-humanized-mouse-liver-models
#16
Edwin C Y Chow, Holly P Quach, Yueping Zhang, Jason Z Y Wang, David C Evans, Albert P Li, Jose Silva, Rommel G Tirona, Yurong Lai, K Sandy Pang
The humanized liver mouse model is being exploited increasingly for human drug metabolism studies. However, its model stability, intercommunication between human hepatocytes and mouse nonparenchymal cells in liver and murine intestine, and changes in extrahepatic transporter and enzyme expressions have not been investigated. We examined these issues in FRGN [fumarylacetoacetate hydrolase (Fah-/-), recombination activating gene 2 (Rag2-/-), and interleukin 2 receptor subunit gamma (IL-2rg -/-) triple knockout] on nonobese diabetic (NOD) background] and chimeric mice: mFRGN and hFRGN (repopulated with mouse or human hepatocytes, respectively)...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27767181/efficient-recellularisation-of-decellularised-whole-liver-grafts-using-biliary-tree-and-foetal-hepatocytes
#17
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
https://www.readbyqxmd.com/read/27755169/emerging-advancements-in-liver-regeneration-and-organogenesis-as-tools-for-liver-replacement
#18
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
https://www.readbyqxmd.com/read/27684205/generation-of-a-humanized-mouse-liver-using-human-hepatic-stem-cells
#19
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
https://www.readbyqxmd.com/read/27649781/differential-requirements-for-the-canonical-nf-%C3%AE%C2%BAb-transcription-factors-c-rel-and-rela-during-the-generation-and-activation-of-mature-b-cells
#20
Maja Milanovic, Nicole Heise, Nilushi S De Silva, Michael M Anderson, Kathryn Silva, Amanda Carette, Fabiano Orelli, Govind Bhagat, Ulf Klein
Signaling through the canonical nuclear factor-κB (NF-κB) pathway is critical for the generation and maintenance of mature B cells and for antigen-dependent B-cell activation. c-REL (rel) and RELA (rela) are the downstream transcriptional activators of the canonical NF-κB pathway. Studies of B cells derived from constitutional rel knockout mice and chimeric mice repopulated with rela(-/-) fetal liver cells provided evidence that the subunits can have distinct roles during B-cell development. However, the B cell-intrinsic functions of c-REL and RELA during B-cell generation and antigen-dependent B-cell activation have not been determined in vivo...
October 18, 2016: Immunology and Cell Biology
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