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liver repopulation

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https://www.readbyqxmd.com/read/27882948/the-non-canonical-wnt-receptor-ryk-regulates-hematopoietic-stem-cell-repopulation-in-part-by-controlling-proliferation-and-apoptosis
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
Edwin C Y Chow, Holly P Quach, Yueping Zhang, Jason Z Y Wang, David C Evan, Albert P Li, Jose Silva, Rommel G Tirona, Yurong Lai, K Sandy Pang
The humanized liver mouse model is increasingly being exploited for human drug metabolism studies. However, its model stability, inter-communication between human hepatocytes and mouse non-parenchymal cells in liver and murine intestine, and changes in extrahepatic transporter and enzyme expression has not been investigated. We examined these issues in FRGN [Fah(-/-), Rag2(-/-), and IL-2rg(-/-) on NOD background] and chimeric mice: mFRGN, and hFRGN (repopulated with mouse or human hepatocytes, respectively)...
October 27, 2016: 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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27628483/hypoxia-driven-hif2a-coordinates-mouse-liver-regeneration-by-coupling-parenchymal-growth-to-vascular-expansion
#14
Philipp Kron, Michael Linecker, Perparim Limani, Andrea Schlegel, Patryk Kambakamba, Jean-Marie Lehn, Claude Nicolau, Rolf Graf, Bostjan Humar, Pierre-Alain Clavien
: Interaction between sinusoidal endothelial cells and hepatocytes is a prerequisite for liver function. Upon tissue loss, both liver cell populations need to be regenerated. Repopulation occurs in a coordinated pattern, first through the regeneration of parenchyme (hepatocytes), which then produces vascular endothelial growth factor (VEGF) to enable the subsequent angiogenic phase. The signals that instruct hepatocytes to induce timely VEGF remain unidentified. Given that liver is highly vascularized, we reasoned that fluctuations in oxygenation after tissue loss may contribute to the coordination between hepatocyte and sinusoidal endothelial cell proliferation...
September 15, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27569723/combination-of-mass-cytometry-and-imaging-analysis-reveals%C3%A2-origin-location-and-functional-repopulation-of%C3%A2-liver%C3%A2-myeloid-cells-in-mice
#15
Bruna Araujo David, Rafael Machado Rezende, Maísa Mota Antunes, Mônica Morais Santos, Maria Alice Freitas Lopes, Ariane Barros Diniz, Rafaela Vaz Sousa Pereira, Sarah Cozzer Marchesi, Débora Moreira Alvarenga, Brenda Naemi Nakagaki, Alan Moreira Araújo, Daniela Silva Dos Reis, Renata Monti Rocha, Pedro Elias Marques, Woo-Yong Lee, Justin Deniset, Pei Xiong Liew, Stephen Rubino, Laura Cox, Vanessa Pinho, Thiago Mattar Cunha, Gabriel Rocha Fernandes, André Gustavo Oliveira, Mauro Martins Teixeira, Paul Kubes, Gustavo Batista Menezes
BACKGROUND & AIMS: Resident macrophages are derived from yolk sac precursors and seed the liver during embryogenesis. Native cells may be replaced by bone marrow precursors during extensive injuries, irradiation, and infections. We investigated the liver populations of myeloid immune cells and their location, as well as the dynamics of phagocyte repopulation after full depletion. The effects on liver function due to the substitution of original phagocytes by bone marrow-derived surrogates were also examined...
December 2016: Gastroenterology
https://www.readbyqxmd.com/read/27535619/pharmacological-targeting-of-kinases-mst1-and-mst2-augments-tissue-repair-and-regeneration
#16
Fuqin Fan, Zhixiang He, Lu-Lu Kong, Qinghua Chen, Quan Yuan, Shihao Zhang, Jinjin Ye, Hao Liu, Xiufeng Sun, Jing Geng, Lunzhi Yuan, Lixin Hong, Chen Xiao, Weiji Zhang, Xihuan Sun, Yunzhan Li, Ping Wang, Lihong Huang, Xinrui Wu, Zhiliang Ji, Qiao Wu, Ning-Shao Xia, Nathanael S Gray, Lanfen Chen, Cai-Hong Yun, Xianming Deng, Dawang Zhou
Tissue repair and regenerative medicine address the important medical needs to replace damaged tissue with functional tissue. Most regenerative medicine strategies have focused on delivering biomaterials and cells, yet there is the untapped potential for drug-induced regeneration with good specificity and safety profiles. The Hippo pathway is a key regulator of organ size and regeneration by inhibiting cell proliferation and promoting apoptosis. Kinases MST1 and MST2 (MST1/2), the mammalian Hippo orthologs, are central components of this pathway and are, therefore, strong target candidates for pharmacologically induced tissue regeneration...
August 17, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27533015/cellular-barcoding-links-b-1a-b-cell-potential-to-a-fetal-hematopoietic-stem-cell-state-at-the-single-cell-level
#17
Trine A Kristiansen, Elin Jaensson Gyllenbäck, Alya Zriwil, Tomas Björklund, Jeremy A Daniel, Ewa Sitnicka, Shamit Soneji, David Bryder, Joan Yuan
Hematopoietic stem cells (HSCs) undergo a functional switch in neonatal mice hallmarked by a decrease in self-renewing divisions and entry into quiescence. Here, we investigated whether the developmental attenuation of B-1a cell output is a consequence of a shift in stem cell state during ontogeny. Using cellular barcoding for in vivo single-cell fate analyses, we found that fetal liver definitive HSCs gave rise to both B-1a and B-2 cells. Whereas B-1a potential diminished in all HSCs with time, B-2 output was maintained...
August 16, 2016: Immunity
https://www.readbyqxmd.com/read/27510266/efficient-liver-repopulation-of-transplanted-hepatocyte-prevents-cirrhosis-in-a-rat-model-of-hereditary-tyrosinemia-type-i
#18
Ludi Zhang, Yanjiao Shao, Lu Li, Feng Tian, Jin Cen, Xiaotao Chen, Dan Hu, Yan Zhou, Weifen Xie, Yunwen Zheng, Yuan Ji, Mingyao Liu, Dali Li, Lijian Hui
Hereditary tyrosinemia type I (HT1) is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (Fah). Fah-deficient mice and pigs are phenotypically analogous to human HT1, but do not recapitulate all the chronic features of the human disorder, especially liver fibrosis and cirrhosis. Rats as an important model organism for biomedical research have many advantages over other animal models. Genome engineering in rats is limited till the availability of new gene editing technologies. Using the recently developed CRISPR/Cas9 technique, we generated Fah(-/-) rats...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27464750/curative-ex-vivo-liver-directed-gene-therapy-in-a-pig-model-of-hereditary-tyrosinemia-type-1
#19
Raymond D Hickey, Shennen A Mao, Jaime Glorioso, Faysal Elgilani, Bruce Amiot, Harvey Chen, Piero Rinaldo, Ronald Marler, Huailei Jiang, Timothy R DeGrado, Lukkana Suksanpaisan, Michael K O'Connor, Brittany L Freeman, Samar H Ibrahim, Kah Whye Peng, Cary O Harding, Chak-Sum Ho, Markus Grompe, Yasuhiro Ikeda, Joseph B Lillegard, Stephen J Russell, Scott L Nyberg
We tested the hypothesis that ex vivo hepatocyte gene therapy can correct the metabolic disorder in fumarylacetoacetate hydrolase-deficient (Fah(-/-)) pigs, a large animal model of hereditary tyrosinemia type 1 (HT1). Recipient Fah(-/-) pigs underwent partial liver resection and hepatocyte isolation by collagenase digestion. Hepatocytes were transduced with one or both of the lentiviral vectors expressing the therapeutic Fah and the reporter sodium-iodide symporter (Nis) genes under control of the thyroxine-binding globulin promoter...
July 27, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27459202/bioengineered-livers-a-new-tool-for-drug-testing-and-a-promising-solution-to-meet-the-growing-demand-for-donor-organs
#20
Franziska Mußbach, Utz Settmacher, Olaf Dirsch, Chichi Xie, Uta Dahmen
BACKGROUND: Organ engineering is a new innovative strategy to cope with two problems: the need for physiological models for pharmacological research and donor organs for transplantation. A functional scaffold is generated from explanted organs by removing all cells (decellularization) by perfusing the organ with ionic or nonionic detergents via the vascular system. Subsequently the acellular scaffold is reseeded with organ-specific cells (repopulation) to generate a functional organ. SUMMARY: This review gives an overview of the state of the art describing the decellularization process, the subsequent quality assessment, the repopulation techniques and the functional assessment...
July 27, 2016: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
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