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https://www.readbyqxmd.com/read/28738402/biodistribution-of-liver-derived-mesenchymal-stem-cells-after-peripheral-injection-in-a-hemophilia-a-patient
#1
Etienne M Sokal, Catherine Anne Lombard, Véronique Roelants, Mustapha Najimi, Sharat Varma, Camillo Sargiacomo, Joachim Ravau, Giuseppe Mazza, François Jamar, Julia Versavau, Vanessa Jacobs, Marc Jacquemin, Stéphane Eeckhoudt, Catherine Lambert, Xavier Stéphenne, Françoise Smets, Cédric Hermans
BACKGROUND: With the exception of liver transplantation, there is no cure for hemophilia, which is currently managed by preemptive replacement therapy. Liver-derived stem cells are in clinical development for inborn and acquired liver diseases and could represent a curative treatment for hemophilia A. The liver is a major factor VIII (FVIII) synthesis site, and mesenchymal stem cells have been shown to control joint bleeding in animal models of hemophilia. Adult-derived human liver stem cells (ADHLSCs) have mesenchymal characteristics and have been shown able to engraft in and repopulate both animal and human livers...
August 2017: Transplantation
https://www.readbyqxmd.com/read/28735385/preparation-of-decellularized-liver-scaffolds-and-recellularized-liver-grafts
#2
Yibin Chen, Sharon Geerts, Maria Jaramillo, Basak E Uygun
Severe liver disease is the 12th leading cause of death in the USA, with organ transplantation often being the only viable option for treatment. However, due to the shortage of viable donor livers, it is estimated that over 1200 patients died in 2015 while waiting for liver transplantation. This highlights the need for alternative sources of viable organs. In this study, we describe a method that provides the groundwork for the development of functional liver grafts. The approach described here is for removal of cells from intact livers and subsequently repopulating them with functional liver cells...
July 23, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28717194/rapid-production-of-human-liver-scaffolds-for-functional-tissue-engineering-by-high-shear-stress-oscillation-decellularization
#3
Giuseppe Mazza, Walid Al-Akkad, Andrea Telese, Lisa Longato, Luca Urbani, Benjamin Robinson, Andrew Hall, Kenny Kong, Luca Frenguelli, Giusi Marrone, Oliver Willacy, Mohsen Shaeri, Alan Burns, Massimo Malago, Janet Gilbertson, Nigel Rendell, Kevin Moore, David Hughes, Ioan Notingher, Gavin Jell, Armando Del Rio Hernandez, Paolo De Coppi, Krista Rombouts, Massimo Pinzani
The development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of a new methodology for the rapid and accurate production of human acellular liver tissue cubes (ALTCs) using normal liver tissue unsuitable for transplantation. The application of high shear stress is a key methodological determinant accelerating the process of tissue decellularization while maintaining ECM protein composition, 3D-architecture and physico-chemical properties of the native tissue...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694332/the-ets2-repressor-factor-erf-is-required-for-effective-primitive-and-definitive-hematopoiesis
#4
Ioanna Peraki, James Palis, George Mavrothalassitis
Erf is a ubiquitously expressed ets-DNA-binding containing transcriptional repressor. Erf haploinsufficiency causes craniosynostosis in human and mice, while its absence in mice leads to failed chorioallantoic fusion and death at E10.5. In this study, we show that Erf is required in all three waves of embryonic hematopoiesis. Mice lacking Erf in embryo proper exhibited severe anemia and died around embryonic day (E) 14.5. Erf epiblast specific knockout embryos had reduced numbers of circulating blood cells from E9...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28659616/a-novel-humanized-mouse-lacking-murine-p450-oxidoreductase-for-studying-human-drug-metabolism
#5
Mercedes Barzi, Francis P Pankowicz, Barry Zorman, Xing Liu, Xavier Legras, Diane Yang, Malgorzata Borowiak, Beatrice Bissig-Choisat, Pavel Sumazin, Feng Li, Karl-Dimiter Bissig
Only one out of 10 drugs in development passes clinical trials. Many fail because experimental animal models poorly predict human xenobiotic metabolism. Human liver chimeric mice are a step forward in this regard, as the human hepatocytes in chimeric livers generate human metabolites, but the remaining murine hepatocytes contain an expanded set of P450 cytochromes that form the major class of drug-metabolizing enzymes. We therefore generated a conditional knock-out of the NADPH-P450 oxidoreductase (Por) gene combined with Il2rg (- /-) /Rag2 (- /-) /Fah (- /-) (PIRF) mice...
June 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28535778/exosomes-from-mesenchymal-stem-cells-induce-the-conversion-of-hepatocytes-into-progenitor-oval-cells
#6
Hao-Hsiang Wu, Oscar K Lee
BACKGROUND: We previously reported that mesenchymal stem cells (MSCs) possess therapeutic effects in a murine model of carbon tetrachloride-induced acute liver failure. In the study, we observed that the majority of repopulated hepatocytes were of recipient origin and were adjacent to transplanted MSCs; only a low percentage of repopulated hepatocytes were from transplanted MSCs. The findings indicate that MSCs guided the formation of new hepatocytes. Exosomes are important messengers for paracrine signaling delivery...
May 23, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28460567/human-mesenchymal-stem-cells-partially-reverse-infertility-in-chemotherapy-induced-ovarian-failure
#7
Sara A Mohamed, Shahinaz M Shalaby, Mohamed Abdelaziz, Soumia Brakta, William D Hill, Nahed Ismail, Ayman Al-Hendy
INTRODUCTION: Chemotherapy is the most commonly used modality to treat human cancers; however, in many cases it causes irreversible ovarian failure. In this work, we plan to evaluate the restorative function of human bone marrow mesenchymal stem cells (BMSCs) in a chemotherapy-induced ovarian failure mouse model. METHODS: Acclimatized 4 to 6 week-old female mice (C57BL/6) were assigned randomly to a vehicle-treated control group (group 1), chemotherapy-treated group followed by vehicle alone (group 2), or chemotherapy-treated group followed by stem cell intraovarian injection (group 3)...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28407125/cell-fate-modification-toward-the-hepatic-lineage-by-extrinsic-factors
#8
Masaki Kawamata, Atsushi Suzuki
The lineage of a somatic cell can be altered by targeting its signaling networks with small molecules and/or genetically altering the expression of key transcription factors. Depending on the combination of factors, fibroblasts can be fully reprogrammed into induced pluripotent stem (iPS) cells or directly converted into specific cell lineages, bypassing the pluripotent state. The generation of defined target cells will enormously benefit patients who require cell transplantation therapy. In the decade since iPS cells were first generated, many cell types have been induced from fibroblasts by direct conversion, including hepatocytes...
April 12, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28389020/seeds-in-the-liver
#9
REVIEW
Hongjie Ji, Yanrong Lu, Yujun Shi
The liver is a crucial organ for homeostasis and has a tremendous self-renewal and regenerative capacity. It has long been believed that the self-renewal and repair of the liver within a given physiological condition or its repopulation in chronic liver diseases, when hepatocyte proliferation is impaired, will primarily be conducted by the proliferating duct cells, termed "oval cells" or hepatic progenitor cells (HPCs). In addition, numerous studies have revealed that HPCs are the initial tumor cells of liver cancer under certain micro-environments...
May 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28372287/organ-reconstruction-dream-or-reality-for%C3%A2-the%C3%A2-future
#10
REVIEW
J-F Stoltz, L Zhang, J S Ye, N De Isla
The relevance of research on reconstructed organs is justified by the lack of organs available for transplant and the growing needs for the ageing population. The development of a reconstructed organ involves two parallel complementary steps: de-cellularization of the organ with the need to maintain the structural integrity of the extracellular matrix and vascular network and re-cellularization of the scaffold with stem cells or resident cells.Whole organ engineering for liver, heart, lung or kidneys, is particularly difficult because of the structural complexity of organs and heterogeneity of cells...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28214206/involvement-of-prolyl-isomerase-pin1-in-the-cell-cycle-progression-and-proliferation-of-hepatic-oval-cells
#11
Prabodh Risal, Nirajan Shrestha, Lokendra Chand, Karl G Sylvester, Yeon Jun Jeong
Liver regenerates remarkably after toxic injury or surgical resection. In the case of failure of resident hepatocytes to restore loss, repopulation is carried out by induction, proliferation, and differentiation of the progenitor cell. Although, some signaling pathways have been verified to contribute oval cell-mediated liver regeneration, role of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1(Pin1) in the oval cells proliferation is unknown. In the present study, we evaluate the role of Pin1 in oval cells proliferation...
January 18, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28162155/-three-dimensional-circulation-perfusion-culture-of-hepatocytes-in-the-liver-decellularizedscaffold
#12
L Wang, P C Zhou, S S Zhu, Y Wang, X J Fan, M Y Zhu, Z W Wang, H X Qian
Objective: The intact rat liver decellularized scaffolds were preparedand repopulated hepatocytes by continuous perfusion technology.Toprovideexperimental support for the application of decellularized liver scaffolds in liver engineering. Method: Decellularized liver scaffolds were obtained by perfusing method. The composition and structure was examined by HE, Masson, Sirius red stain and immunofluorescence. The ultrastructure was examined by scanning electron microscope (SEM). DNA content was used to confirm the effect of decellularization...
January 24, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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
#13
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...
March 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28053091/fumarylacetoacetate-hydrolase-knock-out-rabbit-model-for-hereditary-tyrosinemia-type-1
#14
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-cyclohexanedione (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone...
March 17, 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
#15
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)...
January 2, 2017: 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
#16
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-identify-novel-regulators-of-hematopoietic-stem-cell-function
#17
Javed K Manesia, Monica Franch, Daniel Tabas-Madrid, Ruben Nogales-Cadenas, Thomas Vanwelden, Elisa Van Den Bosch, Zhuofei Xu, Alberto Pascual-Montano, Satish Khurana, Catherine M Verfaillie
During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, whereas 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...
April 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/27957815/evolution-of-graft-morphology-and-function-after-recellularization-of-decellularized-rat-livers
#18
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
#19
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...
April 2017: 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
#20
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
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