Normal atmospheric oxygen tension and the use of antioxidants improve hepatocyte spheroid viability and function.

Abstract:

:Hepatocyte spheroids have been proposed for drug metabolism studies and in bioartificial liver devices. However, the optimal conditions required to meet the aerobic demands of mitochondria-rich hepatocyte spheroids is not well studied. We hypothesized that an optimal concentration of oxygen could be identified and that the health of hepatocyte spheroids might be further improved by antioxidant therapy. Rat hepatocyte spheroids were maintained in suspension culture for 7 days under a mixture of 5% CO(2) plus O(2):N(2) to achieve fractional oxygen contents of 6%(C1), 21%(C2), 58%(C3), and 95%(C4). Spheroid health was assessed under each condition by vital staining, TEM, oxygen consumption, and mitochondrial counts. Hepatocyte differentiation was assessed by expression of 10 liver-related genes (HNF4a, HNF6, Cyp1A1, albumin, Nags, Cps1, Otc, Ass, Asl, Arg1). Functional markers (albumin and urea) were measured. The influence of oxygen tension and antioxidant treatment on the production of reactive oxygen species (ROS) was assessed by confocal microscopy. We observed that the hepatocyte spheroids were healthiest under normal atmospheric (C2) conditions with antioxidants ascorbic acid and L-carnitine. Cell death and reduced functionality of hepatocyte spheroids correlated with the formation of ROS. Normal atmospheric conditions provided the optimal oxygen tension for suspension culture of hepatocyte spheroids. The formation and deleterious effects of ROS were further reduced by adding antioxidants to the culture medium. These findings have direct application to development of the spheroid reservoir bioartificial liver and the use of hepatocyte spheroids in drug metabolism studies.

journal_name

J Cell Physiol

authors

Lillegard JB,Fisher JE,Nedredal G,Luebke-Wheeler J,Bao J,Wang W,Amoit B,Nyberg SL

doi

10.1002/jcp.22651

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

2987-96

issue

11

eissn

0021-9541

issn

1097-4652

journal_volume

226

pub_type

杂志文章
  • Rapid inverse changes in alpha 1B- and beta 2-adrenergic receptors and gene transcripts in acutely isolated rat liver cells.

    abstract::In vitro incubation of hepatocytes acutely isolated from adult male rats leads to a rapid conversion of the adrenergic activation of glycogenolysis from an alpha 1-receptor (alpha 1AR) to a beta 2-receptor (beta 2AR) mediated response within 4 h. In order to understand the underlying mechanism, we examined time-depend...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041520111

    authors: Ishac EJ,Lazar-Wesley E,Kunos G

    更新日期:1992-07-01 00:00:00

  • Regulation of Cu,Zn-superoxide dismutase in bovine pulmonary artery endothelial cells.

    abstract::To evaluate the regulation of endothelial cell Cu,Zn-SOD, we have exposed bovine pulmonary artery endothelial cells in culture to hyperoxia and hypoxia, second messengers or related agonists, hormones, free radical generating systems, endotoxin, and cytokines and have measured Cu,Zn-SOD protein of these cells by an EL...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041530308

    authors: Kong XJ,Fanburg BL

    更新日期:1992-12-01 00:00:00

  • Increased epidermal growth factor receptor in an estrogen-responsive, adriamycin-resistant MCF-7 cell line.

    abstract::We examined the expression of the estrogen and epidermal growth factor (EGF) receptors in a drug-resistant subline of MCF-7 cells in order to study potential alterations in hormone dependence or in the growth factor pathway that could be related to the development of drug resistance in human breast cancer. The drug-re...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041570115

    authors: Dickstein B,Valverius EM,Wosikowski K,Saceda M,Pearson JW,Martin MB,Bates SE

    更新日期:1993-10-01 00:00:00

  • Role of cyclic-AMP responsive element binding (CREB) proteins in cell proliferation in a rat model of hepatocellular carcinoma.

    abstract::The role of cyclic adenosine monophosphate (cAMP) is poorly understood in the regulation of normal and abnormal hepatic cell growth. In this study, we examined the regulation of intracellular cAMP levels and its effect on nuclear cAMP responsive elements (CREs) in a rat model of hepatocellular carcinoma (HCC). Tumorig...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.20474

    authors: Kovach SJ,Price JA,Shaw CM,Theodorakis NG,McKillop IH

    更新日期:2006-02-01 00:00:00

  • Exosomes are the novel players involved in the beneficial effects of exercise on type 2 diabetes.

    abstract::Exosomes contain regulatory signals such as lipids, proteins, and nucleic acids which can be transferred to adjacent or remote cells to mediate cell-to-cell communication. Exercise is a positive lifestyle for metabolic health and a nonpharmacological treatment of insulin resistance and metabolic diseases. Moreover, ex...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章,评审

    doi:10.1002/jcp.28319

    authors: Li G,Liu H,Ma C,Chen Y,Wang J,Yang Y

    更新日期:2019-02-12 00:00:00

  • Cell growth and differentiation in vitro in mouse macrophages transformed by a tsA mutant of simian virus 40. I. Cellular response in proliferative and phagocytic activities to the shift of temperature differs depending on the culture state in mouse bone

    abstract::It was shown previously that mouse bone marrow cells transformed by simian virus 40 (SV40) show a reversible cell density-dependent phenotypic transition between the nonmacrophage (rapidly growing) and the macrophage (stationary) states; cells in low-density cultures are in the growing phase, express SV40 T antigen st...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041160307

    authors: Tanigawa T,Takayama H,Takagi A,Kimura G

    更新日期:1983-09-01 00:00:00

  • De novo expression of pp125FAK in human macrophages regulates CSK distribution and MAP kinase activation but does not affect focal contact structure.

    abstract::The protein tyrosine kinase pp125FAK (focal adhesion kinase, or FAK) is expressed by a variety of cell types and has been implicated in integrin-mediated signaling events. We explored the potential functions of FAK by expressing it de novo in a cell type lacking FAK. We showed previously that cultured human macrophage...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-4652(199902)178:2<164::AID-JCP5

    authors: De Nichilo MO,Katz BZ,O'Connell B,Yamada KM

    更新日期:1999-02-01 00:00:00

  • Aluminum fluoride stimulates inositol phosphate metabolism and inhibits expression of differentiation markers in mouse keratinocytes.

    abstract::Mouse keratinocytes are induced to differentiate in vitro by elevating the level of extracellular calcium from 0.05 mM, where keratinocytes express a basal cell phenotype, to greater than 0.10 mM, where they express the differentiated phenotype. This process has been associated with a rapid, sustained increase in inos...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041480113

    authors: Lee E,Yuspa SH

    更新日期:1991-07-01 00:00:00

  • TGF-beta-induced G2/M delay in proliferating rabbit articular chondrocytes is associated with an enhancement of replication rate and a cAMP decrease: possible involvement of pertussis toxin-sensitive pathway.

    abstract::This study was undertaken to gain more insight into the mechanism whereby TGF-beta influences the cell cycle progression of cultured rabbit articular chondrocytes. Using proliferating chondrocytes in fetal calf serum-containing medium, we have previously shown that TGF-beta induced a recruitment of cells at the end of...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041500211

    authors: Vivien D,Galéra P,Lebrun E,Daireaux M,Loyau G,Pujol JP

    更新日期:1992-02-01 00:00:00

  • Evolving strategies for global gene expression analysis of cancer.

    abstract::The advent of high throughput gene expression profiling, from microarrays to sequence based assays has yielded vast insight into the biology of tumors. New technologies are constantly being unveiled which promise to generate more accurate maps of tumor gene deregulation, and demand the development of new strategies in...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章,评审

    doi:10.1002/jcp.21554

    authors: Coe BP,Chari R,Lockwood WW,Lam WL

    更新日期:2008-12-01 00:00:00

  • Relationship between c-Kit expression and proliferation in acute myeloblastic leukemia cell lines.

    abstract::We have proposed that the transmembrane receptor encoded by the c-Kit protooncogene and its ligand play an important role in regulating the proliferation of blasts cells in acute myeloblastic leukemia (AML). To test this hypothesis, immunobeads were used to separate blasts from three Kit-expression positive cell lines...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041540225

    authors: Tohda S,Yang GS,Ashman LK,McCulloch EA,Minden MD

    更新日期:1993-02-01 00:00:00

  • Nemo-like kinase regulates postnatal skeletal homeostasis.

    abstract::Nemo-like kinase (Nlk) is related to the mitogen-activated protein (MAP) kinases and known to regulate signaling pathways involved in osteoblastogenesis. In vitro Nlk suppresses osteoblastogenesis, but the consequences of the Nlk inactivation in the skeleton in vivo are unknown. To study the function of Nlk, Nlk(loxP/...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.24625

    authors: Canalis E,Kranz L,Zanotti S

    更新日期:2014-11-01 00:00:00

  • Ontogeny of human neutrophil granulocyte alkaline phosphatase.

    abstract::Human embryonic neutrophils (N) in the liver (from 8.5 mm crown-rump length) are alkaline phosphatase (AP) negative during the first trimester of pregnancy. Early bone marrow granulocytes (from eleventh to sixteenth weeks of gestation) behave similarly. Only a small percentage of slightly AP positive cells could be fo...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1040950313

    authors: Kelemen E,Gulya E,Vass K

    更新日期:1978-06-01 00:00:00

  • Induction of heat-shock response and alterations of protein phosphorylation by a novel topoisomerase II inhibitor, withangulatin A, in 9L rat brain tumor cells.

    abstract::Withangulatin A is a newly identified in vitro topoisomerase II inhibitor isolated from the Chinese antitumor herb Physalis angulata. In vivo, it was found to be cytotoxic, capable of suppressing general protein synthesis and of inducing the synthesis of a small set of proteins including those generated by heat-shock ...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041490110

    authors: Lee WC,Lin KY,Chen CM,Chen ZT,Liu HJ,Lai YK

    更新日期:1991-10-01 00:00:00

  • microRNA-related single-nucleotide polymorphisms and breast cancer.

    abstract::Breast cancer, as the most common cancer in women which affects patients both mentally and physically, requires great attention in many areas and many levels as this cancer is known to be multifactorial. Single-stranded molecules called microRNAs with near 22 nucleotides are seen to act in central dogma of molecular b...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章,评审

    doi:10.1002/jcp.29966

    authors: Bahreini F,Rayzan E,Rezaei N

    更新日期:2021-03-01 00:00:00

  • Collagen degradation in human lung fibroblasts: extent of degradation, role of lysosomal proteases, and evaluation of an alternate hypothesis.

    abstract::Experiments were conducted to determine the extent and variability of collagen degradation in human fetal lung fibroblasts. Cells were incubated with [14C]proline, and degradation was measured by determining the hydroxy[14C]proline in a low molecular weight fraction relative to total hydroxy[14C]proline. Average (basa...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041210119

    authors: Bienkowski RS

    更新日期:1984-10-01 00:00:00

  • Regulation of myelin basic protein gene transcription: identification of a distal cis-acting regulatory element.

    abstract::The myelin basic protein (MBP) gene contains sequences located upstream of its transcription start site which play a key role in glial-specific transcription of the MBP promoter. Earlier analysis of the 320 bp upstream regulatory sequence of MBP has revealed multiple cis-acting regulatory motifs which differentially r...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041630213

    authors: Haque NS,Haas S,Knobler RL,Khalili K

    更新日期:1995-05-01 00:00:00

  • Delay of M-phase onset by aphidicolin can retain the nuclear localization of zinc and metallothionein in 3T3-L1 fibroblasts.

    abstract::The transient nuclear localization of metallothionein during cell growth and differentiation may be related to the increased requirement of zinc for DNA synthesis, activation of metalloenzymes, and transcription factors. Treatment of 3T3-L1 fibroblasts with aphidicolin, an inhibitor of nuclear DNA synthesis, caused a ...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-4652(200005)183:2<247::AID-JCP1

    authors: Apostolova MD,Cherian MG

    更新日期:2000-05-01 00:00:00

  • Effect of aging on the mechanisms of PTH-induced calcium influx in rat intestinal cells.

    abstract::We have investigated the effects of aging on parathyroid hormone (PTH) modulation of intracellular calcium homeostasis and their relationship to signal transduction pathways in isolated rat duodenal cells (enterocytes). PTH (10(-8)-10(-9) M) increased enterocyte (45)Ca(2+) influx and intracellular Ca(2+) concentration...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-4652(200003)182:3<429::AID-JCP1

    authors: Massheimer V,Picotto G,Boland R,De Boland AR

    更新日期:2000-03-01 00:00:00

  • Mitochondrial DNA oxidative damage contributes to cardiomyocyte ischemia/reperfusion-injury in rats: cardioprotective role of lycopene.

    abstract::Mitochondrial (mt) dysfunction and oxidative stress are involved in the pathogenesis of ischemia/reperfusion (I/R)-injury. Lycopene, a lipophilic antioxidant found mainly in tomatoes and in other vegetables and fruits, can protect mtDNA against oxidative damage. However, the role of mtDNA in myocardial I/R-injury is u...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.24941

    authors: Yue R,Xia X,Jiang J,Yang D,Han Y,Chen X,Cai Y,Li L,Wang WE,Zeng C

    更新日期:2015-09-01 00:00:00

  • Prereplicative changes in the soluble calmodulin of isoproterenol-activated rat parotid glands.

    abstract::Cells of rat parotid glands were maximally stimulated to initiate DNA synthesis by injecting into the animal a single dose of 25 to 150 mg of isoproterenol/kg of body weight. During the 18- to 21-hr prereplicative period following injection of the highest dose of the drug, there were two predominant and transient redi...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041180307

    authors: Campos Gonzales R,Whitfield JF,Boynton AL,MacManus JP,Rixon RH

    更新日期:1984-03-01 00:00:00

  • miRNA-mediated macrophage behaviors responding to matrix stiffness and ox-LDL.

    abstract::Atherosclerosis is one of the leading causes of morbidity and mortality, mainly due to the immune response triggered by the recruitment of monocytes/macrophages in the artery wall. Accumulating evidence have shown that matrix stiffness and oxidized low-density lipoproteins (ox-LDL) play important roles in atherosclero...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.29543

    authors: Li J,Wang S,Li Y,Zhang N,Gribskov M,Zhang X,Lin M,Shao D,Zhang C,Dai L,Qin C,Duan X,Li J,Xu F,Yang H

    更新日期:2020-09-01 00:00:00

  • Curcumin attenuates proangiogenic and proinflammatory factors in human eutopic endometrial stromal cells through the NF-κB signaling pathway.

    abstract::Endometriosis is a chronic gynecological inflammatory disorder in which immune system dysregulation is thought to play a role in its initiation and progression. Due to altered sex steroid receptor concentrations and other signaling defects, eutopic endometriotic tissues have an attenuated response to progesterone. Thi...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.27360

    authors: Chowdhury I,Banerjee S,Driss A,Xu W,Mehrabi S,Nezhat C,Sidell N,Taylor RN,Thompson WE

    更新日期:2019-05-01 00:00:00

  • Regulation of cellular growth by sodium pump activity.

    abstract::Cellular growth has been found to be directly related to the amount of sodium pumping activity in mouse lymphoblasts (L5178-Y) cultured in varying concentrations of the cardiac glycoside, ouabain. No short-term adaptation (within one generation) occured; i.e., neither growth rate nor (Na+ + K+)-ATPase activity increas...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1040870313

    authors: Shank BB,Smith NE

    更新日期:1976-03-01 00:00:00

  • Exercise training corrects control of spontaneous calcium waves in hearts from myocardial infarction heart failure rats.

    abstract::Impaired cardiac control of intracellular diastolic Ca(2+) gives rise to arrhythmias. Whereas exercise training corrects abnormal cyclic Ca(2+) handling in heart failure, the effect on diastolic Ca(2+) remains unstudied. Here, we studied the effect of exercise training on the generation and propagation of spontaneous ...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.22771

    authors: Kemi OJ,MacQuaide N,Hoydal MA,Ellingsen O,Smith GL,Wisloff U

    更新日期:2012-01-01 00:00:00

  • Inflammation Controls Sensitivity of Human and Mouse Intestinal Epithelial Cells to Galectin-1.

    abstract::Galectins play key roles in the inflammatory cascade. In this study, we aimed to analyze the effect of galectin-1 (Gal-1) in the function of intestinal epithelial cells (IECs) isolated from healthy and inflamed mucosa. IECs isolated from mice or patients with inflammatory bowel diseases (IBD) were incubated with diffe...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.25249

    authors: Muglia CI,Gobbi RP,Smaldini P,Delgado ML,Candia M,Zanuzzi C,Sambuelli A,Rocca A,Toscano MA,Rabinovich GA,Docena GH

    更新日期:2016-07-01 00:00:00

  • Characterization of the D-allose-mediated regulation of sugar transport in Chinese hamster fibroblasts.

    abstract::Exposure to D-allose has been demonstrated to lead to decreased 2-deoxy-D-glucose (2-DG) and 3-0-methyl-D-glucose transport in the V79 Chinese hamster lung fibroblast cell line. The effect of D-allose 1) was maximal after 4 hours exposure to the cells; 2) was optimal between 2.77 and 5.55 mM D-allose; and 3) led to a ...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.1041450217

    authors: Germinario RJ,Kristof A,Chang Z,Manuel S

    更新日期:1990-11-01 00:00:00

  • Overexpression of calreticulin contributes to the development and progression of pancreatic cancer.

    abstract::We studied the clinicopathological significance for Calreticulin (CRT) expression in pancreatic cancer (PC), and its functional relationship with other signaling genes (especially with p53) in regulating the biological behavior of PC cells. IHC, IF, IB, and real-time PCR were used to detect CRT expression in PC, while...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.24519

    authors: Sheng W,Chen C,Dong M,Zhou J,Liu Q,Dong Q,Li F

    更新日期:2014-07-01 00:00:00

  • microRNA-203 promotes proliferation, differentiation, and migration of osteoblasts by upregulation of Msh homeobox 2.

    abstract::Despite the improvements in fracture healing, about 10% of patients undergo abnormal healing. As a tumor suppressor, upregulation of microRNA (miR)-203 has been observed in osteogenic differentiation. Herein, we aimed to explore the functional role of miR-203 in osteoblasts as well as the underlying mechanisms. The ex...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.28387

    authors: Liu H,Chen B,Li Y

    更新日期:2019-08-01 00:00:00

  • HTRA1 expression profile and activity on TGF-β signaling in HTRA1 mutation carriers.

    abstract::High temperature requirement A1 (HTRA1) is a serine protease playing a modulatory role in various cell processes, particularly in the regulation of transforming growth factor-β (TGF-β) signaling. A deleterious role in late-onset cerebral small vessel diseases (CSVDs) of heterozygous HTRA1 mutations, otherwise causativ...

    journal_title:Journal of cellular physiology

    pub_type: 杂志文章

    doi:10.1002/jcp.29609

    authors: Fasano A,Formichi P,Taglia I,Bianchi S,Di Donato I,Battisti C,Federico A,Dotti MT

    更新日期:2020-10-01 00:00:00