DOCSLIB.ORG

A Morphometric Study of the Endoplasmic Reticulum in Human

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Morphometric Study of the Endoplasmic Reticulum in Human Gut: first published as 10.1136/gut.15.9.737 on 1 September 1974. Downloaded from Gut, 1974, 15, 737-747 A morphometric study of the endoplasmic reticulum in human hepatocytes' Correlation between morphological and biochemical data in subjects under treatment with certain drugs A. M. JtZtQUEL2, M. KOCH, AND F. ORLANDI From the Digestive Diseases and Cell Pharmacology Units, University of Ancona School of Medicine, the Centre for the Study of the Action of Drugs on the Liver, University of Camerino, and the Division of Gastroenterology, General Hospital, Ancona, Italy SUMMARY The distribution of the endoplasmic reticulum in human hepatocytes is defined in quanti- tative terms using the techniques of morphometry. The subjects of the study are liver biopsies from normal, untreated subjects and patients being treated with various drugs. In contrast to rat hepato- cytes, the amount of smooth endoplasmic reticulum (SER) in man exceeds that of the rough endo- plasmic reticulum (RER) and accounts for 76.3 % of the total endoplasmic reticulum. This is to be taken into consideration in pharmacological or toxicological studies. In addition, two components of the SER have been identified: more prominent is the type 1 or vesicular which has a regular honeycomb pattern, made up ofcisternae with patent lumina and a mean width of 1500 A; the type 2, or non-vesicular, occurs in discrete foci of densely packed smooth membranes with a spacing of about 140 A. In subjects under short-term treatment with Benzodiazepin (diazepam) the RER re- http://gut.bmj.com/ mained unchanged but the SER membranes were significantly increased with a remarkable, two- to threefold increase of the SER type 2 in three out of four patients. A rise in incorporation of 14C-acetate into digitonin-precipitable sterols as measured in liver biopsy material was also noted in these three patients. The suggestion is made that the SER 2 represents the newly formed mem- branes whereas the SER 1 would represent 'adult' membranes. No changes were observed in two patients under short-term treatment with phenobarbital or Dilantin. on September 23, 2021 by guest. Protected copyright. A few morphometric studies have already been con- the normal base-line data necessary for comparative ducted on animal liver in normal (Loud, 1968; purposes. However, such a study appears essential, Weibel, Staubli, Gnagi, and Hess, 1969; Hess, especially when dealing with toxicological or Weibel, and Preisig, 1973) or in experimental con- pharmacological studies. The subjectivity or the ditions (Wiener, Loud, Kimberg, and Spiro, 1968; aesthetic feelings of the observer often interfere Staubli, Hess, and Weibel, 1969; Hope, 1970; with an objective interpretation of findings and do Riede, Seebass, and Rohr, 1971a; Riede, Strassle, not permit a quantitative estimation of the changes Bianchi, and Rohr, 1971b; Dobbins, Rollins, Brooks, observed. In the present study, we have applied the and Fallon, 1972; Bolender and Weibel, 1973) but technique of Weibel, Kistler, and Scherle (1966) and quantitative analyses of human liver are still lack- Weibel et al (1969) to the study of human liver, ing. Ethical and practical considerations make it using the material obtained by needle biopsy in difficult to collect the material necessary for defining normal, untreated patients and in patients treated with various drugs. Our attention was especially Received for publication 15 May 1974. concentrated on drugs metabolized by microsomal 1Supported by a research grant n. 7300691/04 of the CNR, Rome. 'Please address all correspondence to: Dr A. M. Jz6quel, Division of enzymes, influencing bilirubin or cholesterol metab- Gastroenterology, Ospedale Regionale 60100 Ancona, Italy. olism. We attempted to correlate the biochemical 737 3 Gut: first published as 10.1136/gut.15.9.737 on 1 September 1974. Downloaded from 738 A. M. Jezequel, M. Koch, and F. Orlandi findings with eventual changes in the endoplasmic Electron microscopy reticulum. The biochemical data concerning the For electron microscopy, a small piece of tissue was effect of these drugs on hepatic biosynthesis of cut in 1 mm3 fragments and fixed in 1 % osmium cholesterol as measured on needle biopsies have been tetroxide buffered with Sorensen's phosphate buffer published elsewhere (Bamonti and Dini, 1973; pH 7.4. After dehydration with alcohol and propyl- Orlandi, Bamonti, Dini, Koch, and Jezequel, 1974). ene oxide, the fragments were embedded in a mix- ture of Epon and Araldite. The blocks obtained were Material and Methods cut on a LKB Ultratome III. Thick (1 micron) sections were stained with Azur II-Methylene blue SELECTION OF PATIENTS for examination with the light microscope. Ultra- thin sections were stained with lead citrate and ex- Group 1: Normal untreatedpatients amined with the electron microscope Philips EM Four biopsies of normal, untreated patients were 201. analysed. The selection procedure considered the clinical examination, laboratory findings (BSP re- Quantitative analysis tention at 45 min, SGOT, SGPT, serum bilirubin, For quantitative analysis, five blocks of each biopsy serum alkaline phosphatase). Special attention was material were chosen at random and electron micro- paid to the drug-taking history and only patients graphs from each section were taken on 35 mm film, 'drug-free' for at least three weeks were retained. The first at a magnification of4000 on the screen, ie, 1490 selection also took into account the light micro- on the film due to the reduction in the microscope. scopy findings. The randomization of the areas to be photographed was obtained by placing the screen on the lower Group 2: Treatedpatients without liver involvement left corner of a mesh of the copper grid (Weibel et al, Four patients with normal liver function tests and in 1969). If the angle was not suitable (technical im- need of sedative treatment were given Benzodiazepin perfections, extrahepatocytic space, section edges) (diazepam) according to the following scheme: thestage was movedto another corner. Subsequently, Pe. M. received 20 mg per day for two days; Br. P. the primary magnification was brought to 8600 on received 60 mg per day for three days; Ta. P. and the screen (3200 on film) and 24 500 (9100) without Gi. M. received 40 mg per day for four days. The moving the centre of the picture. Six electron micro- http://gut.bmj.com/ needle biopsy was taken on the morning following graphs were taken at each level of magnification. A the cessation of therapy except in Ta. P. from whom total of 90 pictures was thus obtained for each it was taken at a four-day interval. biopsy. For the purpose of the present study, ie, One patient (Ca. V.) received 50 mg per day of the analysis of the endoplasmic reticulum, measure- diphenylhydantoin (Dilantin) for seven days. A ments were made on pictures taken at a magnifica- biopsy was taken at the beginning oftreatment and is tion of 9100. The films were examined on a project- included in group 1. Another biopsy was taken at ing screen with a secondary tenfold magnification on September 23, 2021 by guest. Protected copyright. the end of the seven-day period. upon which was superimposed a multipurpose test screen with 84 test lines of known length (Weibel et Group 3: Treatedpatient with hepatic dysfunction al, 1966, 1969). The evaluation of the membrane One patient with Gilbert's syndrome and serum bili- surface density Sv ofsmooth androughreticulumwas rubin of 2.06 mg% received 360 mg phenobarbital performed by countingthenumber ofintersections (I) per day for four days. A biopsy was taken before the ofmembrane profiles with the test lines and applying beginning of treatment and another one at the end of the formula Sv = 2 x 1/LT where LT is the length of therapy when the serum bilirubin had fallen to 0.60 the test lines enclosed in the cytoplasm. The results mg%. are expressed in u2 per 3 ofcytoplasm (Weibel et al, 1969). Estimation of the volumetric density (Vv) PROCESSING THE MATERIAL of the endoplasmic reticulum was given by the for- mula Vv = Pp where Pp is the fraction number of The hepatic biosynthesis ofcholesterol endpoints of the test lines enclosed within the pro- This was estimated on biopsy material as described files of the endoplasmic reticulum (Weibel et al, elsewhere (Orlandi et al, 1974). 1969). The mean width (d) of the cisternae was calcu- lated from the volume to surface ratio (v/s) (Weibel Light microscopy et al, 1969) such as v/s = d/2 for the cisternac of the For light microscopy, a fragment of the biopsy was Golgi apparatus which are likened to plates and fixed in formaldehyde, embedded in paraffin, and v/s = d/4 for the rough and smooth endoplasmic stained with haematoxylin-eosin. reticulum which are likened to cylinders. Gut: first published as 10.1136/gut.15.9.737 on 1 September 1974. Downloaded from A morphometric study of the endoplasmic reticulum in human hepatocytes 739 Fig 1 Low-power view ofparenchymal cells ofan untreated subject. In the cyto- plasm, the SER is diffusely distributed and has a regular honeycomb pattern; only the type 1 or vesicular is present. Some RER cisternae are seen in areas free ofglycogen. Numerous mito- chondria (M) contain crystalline formations seen as dense inclusions at this level ofmagnification. The Golgi apparatus (G) is seen next to bile canaliculi (bc) x 7500 http://gut.bmj.com/ on September 23, 2021 by guest. Protected copyright. Results human liver (Ma and Biempica, 1971; Jezequel and Orlandi, 1972; Klion and Schaffner, 1968). We need ELECTRON MICROSCOPY only to insist on the relative paucity of the rough Group 1: normal untreatedpatients endoplasmic reticulum (RER), usually distributed Previous observations have already given a detailed along the nucleus, around or between mitochondria, account of the ultrastructural features of the normal and along the sinusoidal border of the hepatocyte.
Load more

Recommended publications
  • Mft•] ~;;I~ [I) I~ T?L3 ·Ilr!F·S; [,J ~ M
    Mft•] ~;;I~ [I) I~ t?l3 ·ilr!f·S; [,j ~ M Hepatobiliary Imaging Update Maggie Chester and Jerry Glowniak Veterans Affairs Medical Center and Oregon Health Sciences University, Portland, Oregon and the gallbladder ejection fraction (EF) after the injection This is the first article in a four-part series on interventional of cholecystokinin (CCK) (Kinevac®, Squibb Diagnostics, nuclear medicine. Upon completion, the nuclear medicine New Brunswick, NJ). A brief description of the hepatic ex­ technologist should be able to (1) list the advantages of using traction fraction (HEF) was given; the technique used quan­ interventional hepatic imaging, (2) identify the benefit in tifies hepatocyte function more accurately than does excretion calculating HEF, and (3) utilize the HEF calculation method when appropriate. half-time. Since publication of the previous article (5), the HEF has become more widely used as a measure of hepatocyte function, and nearly all the major nuclear medicine software vendors include programs for calculating the HEF. Scintigraphic assessment of hepatobiliary function began in In this article, we will describe new observations and meth­ the 1950s with the introduction of iodine-131 C31 1) Rose ods used in hepatobiliary imaging. The following topics will bengal (1). Due to the poor imaging characteristics of 1311, be discussed: ( 1) the use of morphine as an aid in the diagnosis numerous attempts were made to find a technetium-99m 99 of acute cholecystitis, (2) the rim sign in the diagnosis of acute ( mTc) labeled hepatobiliary agent (2). The most useful of cholecystitis, and (3) methods for calculating the HEF. the several 99mTc-labeled agents that were investigated were the iminodiacetic acid (IDA) analogs, which were introduced MORPHINE-AUGMENTED CHOLESCINTIGRAPHY in the mid 1970s (3).
    [Show full text]
  • Suppression of Hepatocyte CYP1A2 Expression by Kupffer Cells Via Ahr Pathway: the Central Role of Proinflammatory Cytokines
    339-346 29/6/06 12:40 Page 339 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 18: 339-346, 2006 339 Suppression of hepatocyte CYP1A2 expression by Kupffer cells via AhR pathway: The central role of proinflammatory cytokines RONGQIAN WU1, XIAOXUAN CUI1, WEIFENG DONG1, MIAN ZHOU1, H. HANK SIMMS2 and PING WANG1 1Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, NY 11030, USA Received February 6, 2006; Accepted March 23, 2006 Abstract. The hepatic cytochrome P-450 (CYP) enzyme such downregulation. Inhibition of proinflammatory cytokines system provides a major aspect of liver function, yet alterations by curcumin may provide a novel approach to modulate the of CYP in sepsis remain largely unknown. Although we have hepatic CYP function in sepsis. recently shown that CYP1A2, one of the major isoforms of CYP in rats, is downregulated in sepsis, the underlying mech- Introduction anism and possible therapeutic approaches warrant further investigation. The aim of this study was to determine whether Sepsis is the leading cause of death in non-cardiac intensive Kupffer cells (KCs) play any role in suppressing CYP1A2 in care units with >210,000 people succumbing to overwhelming the hepatocytes (HCs) and if so, how to modulate CYP1A2 infection (or the resultant multiple organ failure) in the US expression in sepsis. To study this, primary KCs and HCs annually (1). Although experimental studies using cell and were cultured separately or together with or without transwells. animal models have greatly improved our understanding of Cells and supernatant samples were collected after various the pathophysiology of sepsis, there remains a remarkable stimulations.
    [Show full text]
  • Hepatocyte Growth Factor Signaling Pathway As a Potential Target in Ductal Adenocarcinoma of the Pancreas
    JOP. J Pancreas (Online) 2017 Nov 30; 18(6):448-457. REVIEW ARTICLE Hepatocyte Growth Factor Signaling Pathway as a Potential Target in Ductal Adenocarcinoma of the Pancreas Samra Gafarli, Ming Tian, Felix Rückert Department of Surgery, Medical Faculty Mannheim, University of Heidelberg, Germany ABSTRACT Hepatocyte growth factor is an important cellular signal pathway. The pathway regulates mitogenesis, morphogenesis, cell migration, invasiveness and survival. Hepatocyte growth factor acts through activation of tyrosine kinase receptor c-Met (mesenchymal epithelial transition factor) as the only known ligand. Despite the fact that hepatocyte growth factor is secreted only by mesenchymal origin cells, the targets of this multifunctional pathway are cells of mesenchymal as well as epithelial origin. Besides its physiological role recent evidences suggest that HGF/c-Met also plays a role in tumor pathophysiology. As a “scatter factor” hepatocyte growth factor stimulates cancer cell migration, invasion and subsequently promote metastases. Hepatocyte growth factor further is involved in desmoplastic reaction and consequently indorse chemo- and radiotherapy resistance. Explicitly, this pathway seems to mediate cancer cell aggressiveness and to correlate with poor prognosis and survival rate. Pancreatic Ductal Adenocarcinoma is a carcinoma with high aggressiveness and metastases rate. Latest insights show that the HGF/c-Met signal pathway might play an important role in pancreatic ductal adenocarcinoma pathophysiology. In the present review, we highlight the role of HGF/c-Met pathway in pancreatic ductal adenocarcinoma with focus on its effect on cellular pathophysiology and discuss its role as a potential therapeutic target in pancreatic ductal adenocarcinoma. INTRODUCTION activation causes auto-phosphorylation of c-Met and subsequent activation of downstream signaling pathways Hepatocyte growth factor (HGF) is a multifunctional such as mitogen-activated protein kinases (MAPKs), gene.
    [Show full text]
  • Hepatic Toxicity
    Hepatic Toxicity MSc in Molecular Pathology and Toxicology 2001 Andy Smith MRC Toxicology Unit THE LIVER • The liver constitutes about 5% of the body mass of a rodent or human. • It has many functions eg. Carbohydrate storage and metabolism Synthesis of fibrinogen and albumin etc. Fat metabolism Synthesis of bile acids Metabolism of hormones Formation of urea from amino acids • Blood supply is about 20% arterial-80% venous. • May contain 10-15% of blood volume INFLUENCE OF TOXIC CHEMICALS ON THE LIVER • The liver is the most common site of damage in laboratory animals administered drugs and other chemicals. There are many reasons including the fact that the liver is the first major organ to be exposed to ingested chemicals due to its portal blood supply. • Although chemicals are delivered to the liver to be metabolized and excreted, this can frequently lead to activation and liver injury. • Study of the liver has been and continues to be important in understanding fundamental molecular mechanisms of toxicity as well as in assessment of risks to humans. VENA CAVA HEPATIC VEIN LIVER HEPATIC PORTAL VEIN BILE DUCT SMALL AND LARGE INTESTINE LOBULE PORTAL VEIN BLOOD FLOW HEPATIC ARTERY III I BILE FLOW BILE DUCT CENTRAL VEIN PORTAL TRIAD TYPES OF LIVER CELLS Hepatocytes- Not all the same; depends on lobular site Zone I Higher in respiratory enzymes (periportal) Zone III Higher in cytochrome P450 (centrilobular) Endothelial cells Bile duct cells Oval cells- Possibly stem cells Kupffer cells- Phagocytic cells Important role in inflammation Ito cells- Fat storing or stellate cells TYPES OF HEPATIC INJURY OR RESPONSES Each of the different cell types may respond to a toxic insult.
    [Show full text]
  • Alcohol and Hepatocyte-Kupffer Cell Interaction (Review)
    MOLECULAR MEDICINE REPORTS 4: 597-602, 2011 Alcohol and hepatocyte-Kupffer cell interaction (Review) MICHAEL AJAKAIYE, ASHA JACOB, RONGQIAN WU, JEFFREY M. NICASTRO, GENE F. COPPA and PING WANG Department of Surgery, North Shore University Hospital-Long Island Jewish Medical Center, and Laboratory of Surgical Research, The Feinstein Institute for Medical Research, Manhasset, NY, USA Received December 15, 2010; Accepted March 23, 2011 DOI: 10.3892/mmr.2011.471 Abstract. Alcoholic liver disease accounts for 12,000 deaths 1. Introduction per year in the United States and is the second leading indica- tion for liver transplantation. It covers a spectrum of disease … if the surfeit of delicacies, or the hereditary wine conditions ranging from steatosis and cirrhosis to hepatic of my country dared to disturb my health or the malignancies. Epidemiological data clearly show a strong equilibrium of my poetry, from you, dark monarch, correlation between alcohol consumption and liver diseases. giver of syrups and of poisons, regulator of salts, A large body of evidence has accumulated over the years in from you I hope for justice: I love life: Do not betray determining the molecular mediators of alcohol-induced liver me! Work on! injury. In this review, we provide an overview of such media- —Pablo Neruda, Oda al Higado (1) tors, which include alcohol metabolites and reactive oxygen/ nitrogen species, endotoxin via bacterial translocation from Alcoholic liver disease (ALD) affects 1% of the North the gut and TNF-α, and highlight the role of the sympathetic American population and accounted for over 12,000 deaths in nervous stimuli, norepinephrine and the α2A-adrenergic 2001.
    [Show full text]
  • Nomina Histologica Veterinaria, First Edition
    NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria.
    [Show full text]
  • Pluripotent-Stem-Cell-Derived Hepatic Cells: Hepatocytes and Organoids for Liver Therapy and Regeneration
    cells Review Pluripotent-Stem-Cell-Derived Hepatic Cells: Hepatocytes and Organoids for Liver Therapy and Regeneration Antonietta Messina 1,2,3 , Eléanor Luce 1,2,3, Marwa Hussein 1,2,3 and Anne Dubart-Kupperschmitt 1,2,3,* 1 INSERM unité mixte de recherche (UMR_S) 1193, F-94800 Villejuif, France; [email protected] (A.M.); [email protected] (E.L.); [email protected] (M.H.) 2 UMR_S 1193, Université Paris-Sud/Paris-Saclay, F-94800 Villejuif, France 3 Département Hospitalo-Universitaire (DHU) Hépatinov, F-94800 Villejuif, France * Correspondence: [email protected]; Tel.: +33-145595138 Received: 30 November 2019; Accepted: 10 February 2020; Published: 12 February 2020 Abstract: The liver is a very complex organ that ensures numerous functions; it is thus susceptible to multiple types of damage and dysfunction. Since 1983, orthotopic liver transplantation (OLT) has been considered the only medical solution available to patients when most of their liver function is lost. Unfortunately, the number of patients waiting for OLT is worryingly increasing, and extracorporeal liver support devices are not yet able to counteract the problem. In this review, the current and expected methodologies in liver regeneration are briefly analyzed. In particular, human pluripotent stem cells (hPSCs) as a source of hepatic cells for liver therapy and regeneration are discussed. Principles of hPSC differentiation into hepatocytes are explored, along with the current limitations that have led to the development of 3D culture systems and organoid production. Expected applications of these organoids are discussed with particular attention paid to bio artificial liver (BAL) devices and liver bio-fabrication.
    [Show full text]
  • A Pancreatic Cancer Challenge
    Cancers 2015, 7, 1785-1805; doi:10.3390/cancers7030861 cancersOPEN ACCESS ISSN 2072-6694 www.mdpi.com/journal/cancers Review Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge Wasia Rizwani 1, Amanda E. Allen 2 and Jose G. Trevino 2,* 1 Department of Biochemistry, Osmania University, Hyderabad, Telangana 500007, India; E-Mail: [email protected] 2 Department of Surgery, University of Florida, 1600 SW Archer Rd, Rm 6175, P.O. Box 100109, Gainesville, FL 32610, USA; E-Mail: amanda.allen@ufl.edu * Author to whom correspondence should be addressed; E-Mail: [email protected]fl.edu; Tel.: +1-352-2737-967; Fax: +1-352-2650-761. Academic Editor: Gabriele Multhoff Received: 11 June 2015 / Accepted: 17 August 2015 / Published: 3 September 2015 Abstract: Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression.
    [Show full text]
  • Liver Sinusoidal Endothelial Cells — Gatekeepers of Hepatic Immunity
    REVIEWS Liver sinusoidal endothelial cells — gatekeepers of hepatic immunity Shishir Shetty1,2, Patricia F. Lalor1,2 and David H. Adams1,2* Abstract | Liver sinusoidal endothelial cells (LSECs) line the low shear, sinusoidal capillary channels of the liver and are the most abundant non- parenchymal hepatic cell population. LSECs do not simply form a barrier within the hepatic sinusoids but have vital physiological and immunological functions, including filtration, endocytosis, antigen presentation and leukocyte recruitment. Reflecting these multifunctional properties, LSECs display unique structural and phenotypic features that differentiate them from the capillary endothelium present within other organs. It is now clear that LSECs have a critical role in maintaining immune homeostasis within the liver and in mediating the immune response during acute and chronic liver injury. In this Review , we outline how LSECs influence the immune microenvironment within the liver and discuss their contribution to immune-mediated liver diseases and the complications of fibrosis and carcinogenesis. Sinusoidal endothelial cells line what constitutes a vitelline veins, whereas sinusoids develop from capillary unique vascular bed in the liver, which receives blood vessels of the septum transversum and acquire their from both the hepatic artery and the portal veins into distinctive fenestrated phenotype by week 20 of gesta- the hepatic parenchyma (Fig. 1). Studies of these cells tion7 under the control of transcription factor GATA4 isolated from animals usually refer to them as liver (REF.8). From this point onward, sinusoidal endothelial sinusoidal endothelial cells (LSECs), whereas isolated cells remain functionally and phenotypically distinct human cells have also been referred to as human hepatic from the other vascular endothelial cells in the liver sinusoidal endothelial cells (HSECs).
    [Show full text]
  • Expression of Specific Hepatocyte and Cholangiocyte Transcription Factors
    Laboratory Investigation (2008) 88, 865–872 & 2008 USCAP, Inc All rights reserved 0023-6837/08 $30.00 Expression of specific hepatocyte and cholangiocyte transcription factors in human liver disease and embryonic development Pallavi B Limaye, Gabriela Alarco´n, Andrew L Walls, Michael A Nalesnik, George K Michalopoulos, Anthony J Demetris and Erin R Ochoa Transcription factors are major determinants of cell-specific gene expression in all cell types. Studies in rodent liver have shown that alterations in transcription factor expression determine lineage specification during fetal liver development and signify transdifferentiation of cells of the biliary compartment into ‘oval’ cells and eventually hepatocytes in adult liver. We examined the cellular localization of hepatocyte- or BEC-associated transcription factors in human fetal and adult liver and in diseases in which transdifferentiation between hepatocytes and biliary cells may play a role. In the normal adult human liver, hepatocyte nuclear factor (HNF)4a and HNF6 appeared exclusively in hepatocytes; HNF1b, HNF3a, and HNF3b were observed only in BEC. During fetal development both BEC and hepatocytes expressed HNF3a, HNF3b, and HNF6. HNF1a was expressed only in fetal hepatocytes. We further examined expression of transcription factors in massive hepatic necrosis and in specific types of chronic liver disease. Hepatocyte-associated transcription factors HNF4a and HNF6 also appeared in BEC in massive hepatic necrosis and chronic hepatitis C virus infection. Similarly, HNF3b that is expressed only in BEC in normal adult liver was also observed in hepatocytes in primary biliary cirrhosis and chronic biliary obstruction. These data mimic previous findings in rodents in which hepatocyte-associated transcription factors appear in biliary cells prior to emergence of oval cells, which function as progenitor cells for hepatocytes when the regenerative capacity of the latter is compromised.
    [Show full text]
  • Hepatic Differentiation of Stem Cells in 2D and 3D Biomaterial Systems
    bioengineering Review Hepatic Differentiation of Stem Cells in 2D and 3D Biomaterial Systems Xiaoyu Zhao 1,2, Yanlun Zhu 1,2, Andrew L. Laslett 3,4 and Hon Fai Chan 1,2,* 1 Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China; [email protected] (X.Z.); [email protected] (Y.Z.) 2 Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China 3 CSIRO Manufacturing, Clayton, Victoria 3168, Australia; [email protected] 4 Australian Regenerative Medicine Institute, Monash University, Victoria 3800, Australia * Correspondence: [email protected]; Tel.: +852-39433032 Received: 29 April 2020; Accepted: 22 May 2020; Published: 25 May 2020 Abstract: A critical shortage of donor livers for treating end-stage liver failure signifies the urgent need for alternative treatment options. Hepatocyte-like cells (HLC) derived from various stem cells represent a promising cell source for hepatocyte transplantation, liver tissue engineering, and development of a bioartificial liver assist device. At present, the protocols of hepatic differentiation of stem cells are optimized based on soluble chemical signals introduced in the culture medium and the HLC produced typically retain an immature phenotype. To promote further hepatic differentiation and maturation, biomaterials can be designed to recapitulate cell–extracellular matrix (ECM) interactions in both 2D and 3D configurations. In this review, we will summarize and compare various 2D and 3D biomaterial systems that have been applied to hepatic differentiation, and highlight their roles in presenting biochemical and physical cues to different stem cell sources.
    [Show full text]
  • 26 April 2010 TE Prepublication Page 1 Nomina Generalia General Terms
    26 April 2010 TE PrePublication Page 1 Nomina generalia General terms E1.0.0.0.0.0.1 Modus reproductionis Reproductive mode E1.0.0.0.0.0.2 Reproductio sexualis Sexual reproduction E1.0.0.0.0.0.3 Viviparitas Viviparity E1.0.0.0.0.0.4 Heterogamia Heterogamy E1.0.0.0.0.0.5 Endogamia Endogamy E1.0.0.0.0.0.6 Sequentia reproductionis Reproductive sequence E1.0.0.0.0.0.7 Ovulatio Ovulation E1.0.0.0.0.0.8 Erectio Erection E1.0.0.0.0.0.9 Coitus Coitus; Sexual intercourse E1.0.0.0.0.0.10 Ejaculatio1 Ejaculation E1.0.0.0.0.0.11 Emissio Emission E1.0.0.0.0.0.12 Ejaculatio vera Ejaculation proper E1.0.0.0.0.0.13 Semen Semen; Ejaculate E1.0.0.0.0.0.14 Inseminatio Insemination E1.0.0.0.0.0.15 Fertilisatio Fertilization E1.0.0.0.0.0.16 Fecundatio Fecundation; Impregnation E1.0.0.0.0.0.17 Superfecundatio Superfecundation E1.0.0.0.0.0.18 Superimpregnatio Superimpregnation E1.0.0.0.0.0.19 Superfetatio Superfetation E1.0.0.0.0.0.20 Ontogenesis Ontogeny E1.0.0.0.0.0.21 Ontogenesis praenatalis Prenatal ontogeny E1.0.0.0.0.0.22 Tempus praenatale; Tempus gestationis Prenatal period; Gestation period E1.0.0.0.0.0.23 Vita praenatalis Prenatal life E1.0.0.0.0.0.24 Vita intrauterina Intra-uterine life E1.0.0.0.0.0.25 Embryogenesis2 Embryogenesis; Embryogeny E1.0.0.0.0.0.26 Fetogenesis3 Fetogenesis E1.0.0.0.0.0.27 Tempus natale Birth period E1.0.0.0.0.0.28 Ontogenesis postnatalis Postnatal ontogeny E1.0.0.0.0.0.29 Vita postnatalis Postnatal life E1.0.1.0.0.0.1 Mensurae embryonicae et fetales4 Embryonic and fetal measurements E1.0.1.0.0.0.2 Aetas a fecundatione5 Fertilization
    [Show full text]