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Hepatocyte transplantation

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https://www.readbyqxmd.com/read/28428345/proliferation-of-primary-human-hepatocytes-and-prevention-of-hepatitis-b-virus-reinfection-efficiently-deplete-nuclear-cccdna-in-vivo
#1
Lena Allweiss, Tassilo Volz, Katja Giersch, Janine Kah, Giuseppina Raffa, Joerg Petersen, Ansgar W Lohse, Concetta Beninati, Teresa Pollicino, Stephan Urban, Marc Lütgehetmann, Maura Dandri
OBJECTIVE: The stability of the covalently closed circular DNA (cccDNA) in nuclei of non-dividing hepatocytes represents a key determinant of HBV persistence. Contrarily, studies with animal hepadnaviruses indicated that hepatocyte turnover can reduce cccDNA loads but knowledge on the proliferative capacity of HBV-infected primary human hepatocytes (PHHs) in vivo and the fate of cccDNA in dividing PHHs is still lacking. This study aimed to determine the impact of human hepatocyte division on cccDNA stability in vivo...
April 20, 2017: Gut
https://www.readbyqxmd.com/read/28425419/a-rare-bsep-mutation-associated-with-a-mild-form-of-progressive-familial-intrahepatic-cholestasis-type-2
#2
Orith Waisbourd-Zinman, Lea F Surrey, Anna E Schwartz, Pierre A Russo, Jessica Wen
Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2) is a rare cholestatic disorder diagnosed in infancy or childhood that can lead to severe hepatic fibrosis and liver failure. Mutations in the ABCB11 gene result in a deficiency of the bile salt export protein (BSEP) and accumulation of bile inside the hepatocytes. Hepatocellular carcinoma is another condition associated with severe forms of deletion mutations in the ABCB11 gene. Treatment options including ursodeoxycholic acid biliary diversion have mixed outcomes and some patients require liver transplantation...
May 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28422872/effect-of-hsp27-and-cofilin-in-the-injury-of-hypoxia-reoxygenation-on-hepatocyte-membrane-f-actin-microfilaments
#3
Yafei Zhang, Jiazhong Wang, Hong Ji, Hongwei Lu, Le Lu, Jinlong Wang, Yiming Li
Hypoxia-reoxygenation (H/R) injury hepatocyte models were established to simulate the ischemia/reperfusion injury of transplanted organ. Through the study of the molecular mechanism of H/R on the F-actin damage of the liver cytomembrane, the mechanism of F-actin damage induced by ischemia and reperfusion was studied from the level of cell and molecule.The hypoxic environment of cells in vitro was simulated by chemical hypoxia agent CoCl2. Liver cells were detected by MTT, H/R group was subdivided into 3 subgroups: H/R 2, 4, and 6 h...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28422570/an-induced-adipocyte-sheet-reduces-inflammatory-reactions-during-remodeling-of-xenogeneic-scaffolds-in-vivo
#4
Tong Yi, Qiang Wang, Fan Fan, Gouhui Fan
Surgical therapy of cardiovascular diseases frequently requires replacement of diseased tissues with prosthetic devices or grafts. Calcification is the main reason for the degeneration of implanted grafts. However, some factors reduce stenosis and attenuate calcification of implanted grafts. In this study, we used an autologous induced adipocyte cell-sheet (IACS) as a drug delivery system to determine whether its secretion ability has a beneficial effect on the remodeling process of grafts in a rat subcutaneous model...
April 19, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28420441/autologous-bone-marrow-derived-cell-transplantation-in-decompensated-alcoholic-liver-disease-what-is-the-impact-on-liver-histology-and-gene-expression-patterns
#5
Nicolas Lanthier, Nathalie Lin-Marq, Laura Rubbia-Brandt, Sophie Clément, Nicolas Goossens, Laurent Spahr
BACKGROUND: Liver stem cell therapy (SCT) has been suggested as a promising means to improve liver regeneration in advanced liver disease. However, data from trials are heterogeneous, with no systematic histological evaluation. The aim of this study is to specifically analyze the effect of autologous SCT on liver regeneration and on gene expression changes. METHODS: Individuals in the randomized controlled trial of SCT in alcoholic hepatitis with paired liver biopsies were included (n = 58)...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28415598/caloric-restriction-delays-early-phases-of-carcinogenesis-via-effects-on-the-tissue-microenvironment
#6
Erika Cadoni, Fabio Marongiu, Maura Fanti, Monica Serra, Ezio Laconi
Caloric restriction (CR) is an effective and consistent means to delay aging and the incidence of chronic diseases related to old age, including cancer. However, the precise mechanisms responsible for the beneficial effect of CR on carcinogenic process are yet to be identified.In the present studies the hypothesis was tested that the CR might delay carcinogenesis via modulatory effects exerted on the age-associated, neoplastic-prone tissue microenvironment. Using a well characterized, orthotopic cell transplantation (Tx) system in the rat, preneoplastic hepatocytes isolated from liver nodules were injected into either old syngeneic rats fed ad libitum (AL) or animals of the same age given a CR diet (70% of AL feeding)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414974/bilirubin-nanoparticle-preconditioning-protects-against-hepatic-ischemia-reperfusion-injury
#7
Jin Yong Kim, Dong Yun Lee, Sukmo Kang, Wenjun Miao, Hyungjun Kim, Yonghyun Lee, Sangyong Jon
Hepatic ischemia-reperfusion injury (IRI) remains a major concern in liver transplantation and resection, despite continuing efforts to prevent it. Accumulating evidence suggests that bilirubin possesses antioxidant, anti-inflammatory and anti-apoptotic properties. However, despite obvious potential health benefits of bilirubin, its clinical applications are limited by its poor solubility. We recently developed bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol (PEG)-conjugated bilirubin. Here, we sought to investigate whether BRNPs protect against IRI in the liver by preventing oxidative stress...
April 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28412976/hepatic-population-derived-from-human-pluripotent-stem-cells-is-effectively-increased-by-selective-removal-of-undifferentiated-stem-cells-using-ym155
#8
Seok-Jin Kang, Young-Il Park, So-Ryeon Hwang, Hee Yi, Nga Tham, Hyun-Ok Ku, Jae-Young Song, Hwan-Goo Kang
BACKGROUND: Pluripotent stem cells (PSCs) such as embryonic stem cells and induced pluripotent stem cells are promising target cells for cell regenerative medicine together with recently advanced technology of in-vitro differentiation. However, residual undifferentiated stem cells (USCs) during in-vitro differentiation are considered a potential risk for development of cancer cells and nonspecific lineage cell types. In this study we observed that USCs still exist during hepatic differentiation, consequently resulting in poor quality of the hepatic population and forming teratoma in vivo...
April 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28409921/mesenchymal-stem-cells-seeded-regenerated-silk-fibroin-complex-matrices-for-liver-regeneration-in-an-animal-model-of-acute-liver-failure
#9
Lijuan Xu, Shufang Wang, Xiang Sui, Yu Wang, Yinan Su, Li Huang, Yunwei Zhang, Zheng Chen, Qianqian Chen, Haitao Du, Yaopeng Zhang, Li Yan
The shortage of organ donation is the main limitation to liver transplantation as a treatment for the end-stage liver disease or acute liver failure. In order to develop an alternative therapy for acute liver failure, mesenchymal stem cells (MSCs) seeded regenerated silk fibroin (RSF) matrices were evaluated in vitro and in vivo. Adipose-derived mesenchymal stem cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) were planted and grown on RSF scaffolds to form scaffolds complex, respectively...
April 14, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28409553/the-thyromimetic-kb2115-eprotirome-induces-rat-hepatocyte-proliferation
#10
Marta Szydlowska, Monica Pibiri, Andrea Perra, Elisabetta Puliga, Sandra Mattu, Giovanna Ledda-Columbano, Amedeo Columbano, Vera Leoni
Although the hepatomitogenic activity of T3 is well established, the wide range of harmful effects exerted by this hormone precludes its use in regenerative therapy. The aim of this study was to investigate whether an agonist of TR, KB2115 (Eprotirome) could exert a mitogenic effect in the liver, without most of the adverse T3/TR-dependent side effects. F-344 rats treated with KB2115 for one week displayed a massive increase in bromodeoxyuridine incorporation (from 20 to 40% vs. 5% of controls), which was associated with increased mitotic activity in the absence of significant signs of liver toxicity...
April 13, 2017: Gene Expression
https://www.readbyqxmd.com/read/28407355/extracellular-vesicles-from-bone-marrow-derived-mesenchymal-stem-cells-protect-against-murine-hepatic-ischemia-reperfusion-injury
#11
Hiroaki Haga, Irene K Yan, David Borelli, Akiko Matsuda, Mansi Parasramka, Neha Shukla, David D Lee, Tushar Patel
Hepatic ischemia-reperfusion injury (IRI) and associated inflammation contributes to liver dysfunction and complications after liver surgery and transplantation. Mesenchymal stem cells (MSC) have been reported to reduce hepatic IRI because of their reparative immunomodulatory effects in injured tissues. Recent studies have highlighted beneficial effects of extracellular vesicles from MSCs (MSC-EV) on tissue injury. The effects of systemically administered mouse bone marrow derived MSC-EV were evaluated in an experimental murine model of hepatic IRI induced by cross clamping the hepatic artery and portal vein for 90 minutes followed by reperfusion for periods of upto 6 hours...
April 13, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28407125/cell-fate-modification-toward-the-hepatic-lineage-by-extrinsic-factors
#12
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/28397810/hepatocytic-parental-progenitor-cells-of-rat-small-hepatocytes-maintain-self-renewal-capability-after-long-term-culture
#13
Masayuki Ishii, Junichi Kino, Norihisa Ichinohe, Naoki Tanimizu, Takafumi Ninomiya, Hiromu Suzuki, Toru Mizuguchi, Koichi Hirata, Toshihiro Mitaka
The liver has a variety of functions for maintaining homeostasis, and hepatocytes play a major role. In contrast with the high regenerative capacity of mature hepatocytes (MHs) in vivo, they have not been successfully expanded ex vivo. Here we demonstrate that CD44-positive cells sorted from small hepatocyte (SH) colonies derived from a healthy adult rat liver can proliferate on a Matrigel-coated dish in serum-free chemically defined medium; in addition, a subpopulation of the cells can divide more than 50 times in a period of 17 weeks every 4-week-passage...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28388830/the-release-of-microrna-122-during-liver-preservation-is-associated-with-early-allograft-dysfunction-and-graft-survival-after-transplantation
#14
Jasmijn W Selten, Cornelia J Verhoeven, Veerle Heedfeld, Henk P Roest, Jeroen de Jonge, Jacques Pirenne, Jos van Pelt, Jan N M IJzermans, Diethard Monbaliu, Luc J W van der Laan
INTRODUCTION: Early allograft dysfunction (EAD) after liver transplantation is associated with inferior graft survival. EAD is more prevalent in grafts from donation after circulatory death (DCD). However, accurate prediction of liver function remains difficult due to the lack of specific biomarkers. Recent experimental and clinical studies highlight the potential of hepatocyte-derived microRNAs (miRNAs) as sensitive, stable and specific biomarkers of liver injury. The aim of this study was to determine whether miRNAs in graft preservation fluid are predictive for EAD after clinical liver transplantation and in an experimental DCD model...
April 7, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28386375/expression-of-antisense-of-microrna-26a-5p-in-mesenchymal-stem-cells-increases-their-therapeutic-effects-against-cirrhosis
#15
Li Chen, Wenhuan Zeng, Bo Yang, Xiang Cui, Cong Feng, Lili Wang, Hao Wang, Xuan Zhou, Peng Li, Faqin Lv, Tanshi Li
Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes, and has been shown to prevent cirrhosis during liver regeneration. Transplantation of mesenchymal stem cells (MSCs) reduces the development of cirrhosis after liver injury. However, the production and secretion of transplanted MSCs in liver were not studied yet. Here we found that the MSCs expressed low levels of HGF protein, but surprisingly high levels of HGF mRNA. Further investigation using bioinformatics analyses and luciferase reporter assay showed that MSCs expressed high levels of microRNA-26a-5p (miR-26a-5p), which targeted 3'-UTR of HGF mRNA to inhibit its protein translation...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28386338/pigment-epithelium-derived-factor-pedf-peptide-promotes-the-expansion-of-hepatic-stem-progenitor-cells-via-erk-and-stat3-dependent-signaling
#16
Shou-Chuan Shih, Tsung-Chuan Ho, Show-Li Chen, Yeou-Ping Tsao
Hepatic stem/progenitor cells (HPC) have been considered as a potential cell source of an alternative to liver transplantation. Production of large numbers of autologous HPC from small pieces of live tissue is crucial for the application of HPC-based liver therapy. In this study, we demonstrated that a synthetic 44-amino acid peptide (44-mer) derived from pigment epithelium-derived factor (PEDF) can facilitate the production of a large number of actively dividing HPC from normal adult rat livers in a 35-day culture period...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28386315/protective-benefits-of-amp-activated-protein-kinase-in-hepatic-ischemia-reperfusion-injury
#17
REVIEW
Min Zhang, Dan Yang, Xianqiong Gong, Pu Ge, Jie Dai, Ling Lin, Li Zhang
Hepatic ischemia-reperfusion injury (HIRI) is a major cause of hepatic failure and death after liver trauma, haemorrhagic shock, resection surgery and liver transplantation. AMP-activated protein kinase (AMPK) is an energy sensitive kinase that plays crucial roles in the regulation of metabolic homeostasis. In HIRI, ischemia induces the decline of ATP and the increased ratio of AMP/ATP, which promotes the phosphorylation and activation of AMPK. Three AMPK kinases, liver kinase B1 (LKB1), Ca(2+)/calmodulin-depedent protein kinase kinase β (CaMKKβ) and TGF-β-activated kinase-1 (TAK1), are main upstream kinases for the phosphorylation of AMPK...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28386285/mesenchymal-stem-cells-transplantation-following-partial-hepatectomy-a-new-concept-to-promote-liver-regeneration-systematic-review-of-the-literature-focused-on-experimental-studies-in-rodent-models
#18
REVIEW
Ioannis G Papanikolaou, Charalambos Katselis, Konstantinos Apostolou, Themistoklis Feretis, Maria Lymperi, Manousos M Konstadoulakis, Apostolos E Papalois, George C Zografos
Mesenchymal stem cells (MSCs) are an attractive source for regenerative medicine because they are easily accessible through minimally invasive methods and have the potential to enhance liver regeneration (LG) and improve liver function, following partial hepatectomy (PH) and acute or chronic liver injury. A systematic review of the literature was conducted for articles published up to September 1st, 2016, using the MEDLINE database. The keywords that were used in various combinations were as follows: "Mesenchymal stem cells", "transplantation", "stem cells", "adipose tissue derived stem cells", "bone marrow-derived stem cells", "partial hepatectomy", "acute liver failure", "chronic liver failure", "liver fibrosis", "liver cirrhosis", "rats", "mice", and "liver regeneration"...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28373763/clinical-translation-of-bioartificial-liver-support-systems-with-human-pluripotent-stem-cell-derived-hepatic-cells
#19
REVIEW
Ryoichi Sakiyama, Brandon J Blau, Toshio Miki
There is currently a pressing need for alternative therapies to liver transplantation. The number of patients waiting for a liver transplant is substantially higher than the number of transplantable donor livers, resulting in a long waiting time and a high waiting list mortality. An extracorporeal liver support system is one possible approach to overcome this problem. However, the ideal cell source for developing bioartificial liver (BAL) support systems has yet to be determined. Recent advancements in stem cell technology allow researchers to generate highly functional hepatocyte-like cells from human pluripotent stem cells (hPSCs)...
March 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28372287/organ-reconstruction-dream-or-reality-for%C3%A2-the%C3%A2-future
#20
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
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