Tissue Barriers in Disease, Injury and Regeneration

Tissue Barriers in Disease, Injury and Regeneration focuses on the molecular and cellular fundamentals of homeostatic and defense responses of tissue barriers, covering the damaging impacts and exposure to pathogens and engineered nanomaterials. Sections emphasize the role of mesenchymal stoma, vascular, epithelial, telocyte, myofibroblast, lymphoid and reticuloendothelial cells, along with reactions that bridge the effects of ambient factors, medical treatments, drag delivery systems with alterations in barrier integrity, tissue/organ functions, and metabolic status. Other sections cover the role of progenitor cells of different origins in the remodeling and regeneration of tissue stroma, vasculature of blood-tissue barriers, and more.

• Includes special emphasis on the role of mesenchymal stoma, vascular, epithelial, telocyte, myofibroblast, lymphoid and reticuloendothelial cells in the development of reactions that bridge the effects of ambient factors, medical treatments, drag delivery systems with alterations in barrier integrity, tissue/organ functions, and in metabolic status
• Examines the role of progenitor cells of different origins in the remodeling and regeneration of tissue stroma, the vasculature of blood-tissue barriers, and mucosa and external epithelium

• Language: English
• Publisher: Elsevier Science
• Release date: Jun 19, 2021
• ISBN: 9780128227565

Book preview

Tissue Barriers in Disease, Injury and Regeneration

Editor

Nikolai V. Gorbunov

Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, Maryland 20817, United States

Table of Contents

Cover image

Title page

Copyright

Contributors

Preface

Chapter One. Roles and distribution of telocytes in tissue organization in health and disease

1. Introduction

2. Telocytes—definition and history

3. Localization and identification methods

4. Physiological functions of telocytes

5. Roles of telocytes in disease

6. Perspectives and conclusion

Chapter Two. Effects of radiation on endothelial barrier and vascular integrity

1. Introduction: radiation-induced permeability of the vasculature

2. Direct mechanisms of radiation-induced vascular effects

3. Indirect mechanisms of radiation-induced vascular effects

4. Conclusions

Chapter Three. How severe RNA virus infections such as SARS-CoV-2 disrupt tissue and organ barriers—Reconstitution by mesenchymal stem cell-derived exosomes

1. COVID-19 and the contribution by immune effector cells

2. Immune-mediated pathogenesis

3. Acute lung injury, increased endothelial permeability, and loss of organ barrier function

4. Endogenous repair systems

5. The role of mesenchymal stem cells

6. Extracellular vesicles: Exosomes and small microvesicles

7. Tissue reconstitutive mechanisms by mesenchymal stem cell-small extracellular vesicles in COVID-19

8. Source of exosomes

9. Mesenchymal stem cell-small extracellular vesicles as investigational new drug

10. Exosome enrichment

Chapter Four. The retinal pigment epithelium: at the forefront of the blood-retinal barrier in physiology and disease

1. Introduction

2. Inner blood-retinal barrier

3. Outer blood-retinal barrier

4. Structural changes on optical coherence tomography and fluorescein angiography in the internal blood-retinal barrier and outer blood-retinal barrier in disease states

5. Conclusions

Chapter Five. Appressorium morphogenesis and penetration in rice blast fungus

1. Introduction

2. Appressorium induction and differentiation

3. Appressorium maturation and function

4. Appressorium penetration and invasive growth

5. Conclusion

Chapter Six. Mesenchymal stem cells and exosomes in tissue regeneration and remodeling: characterization and therapy

1. Introduction

2. Mesenchymal stem cell characterization

3. Mesenchymal stem cells and tissue or organ therapy

4. Replacement of mesenchymal stem cells with exosomes including anti-inflammatory cytokines, growth factors, and micro-RNAs

5. Conclusions

Index

Copyright

Elsevier

Radarweg 29, PO Box 211, 1000 AE Amsterdam, Netherlands

The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom

50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States

Copyright © 2021 Elsevier Inc. All rights reserved. This is an open access publication under the CC-BY license (http://creativecommons.org/licenses/BY/4.0/).

This book and the individual contributions contained in it are protected under copyright, and the following terms and conditions apply to their use in addition to the terms of any Creative Commons (CC) or other user license that has been applied by the publisher to an individual chapter:

Photocopying: Single photocopies of single chapters may be made for personal use as allowed by national copyright laws. Permission is not required for photocopying of chapters published under the CC BY license nor for photocopying for non-commercial purposes in accordance with any other user license applied by the publisher. Permission of the publisher and payment of a fee is required for all other photocopying, including multiple or systematic copying, copying for advertising or promotional purposes, resale, and all forms of document delivery. Special rates are available for educational institutions that wish to make photocopies for non-profit educational classroom use.

Derivative works: Users may reproduce tables of contents or prepare lists of chapters including abstracts for internal circulation within their institutions or companies. Other than for chapters published under the CC BY license, permission of the publisher is required for resale or distribution outside the subscribing institution or company. For any subscribed chapters or chapters published under a CC BY-NC-ND license, permission of the publisher is required for all other derivative works, including compilations and translations.

Storage or usage: Except as outlined above or as set out in the relevant user license, no part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior written permission of the publisher.

Permissions: For information on how to seek permission visit http://www.elsevier.com/permissions or call: ([phone] x 3808.

Author rights: Authors may have additional rights in their chapters as set out in their agreement with the publisher (more information at http://www.elsevier.com/authorsrights).

Notices

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Although all advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer.

Library of Congress Cataloging-in-Publication Data

A catalog record for this book is available from the Library of Congress

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library

ISBN: 978-0-12-818561-2

For information on all Elsevier publications visit our website at https://www.elsevier.com/books-and-journals

Publisher: Andre Gerhard Wolff

Acquisitions Editor: Glyn Jones

Editorial Project Manager: Naomi Robertson

Production Project Manager: Paul Prasad Chandramohan

Cover Designer: Matthew Limbert

Cover Image credit: Julian M. Schneider, Ulm University Hospital, Germany

Typeset by TNQ Technologies

Contributors

Taras Ardan,     Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Science, Libechov, Czech Republic

Mădălina Gabriela Barbu,     Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, Bucharest, Romania

Linda Hildegard Bergersen,     Institute for Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway

Andreea Elena Boboc,     Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, Bucharest, Romania

Roxane M. Bouten,     Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

Carmen Elena Condrat,     Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, Bucharest, Romania

Dragoș Crețoiu

Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, Bucharest, Romania

Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Regina M. Day,     Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

Cezara Alina Dănilă,     Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, Bucharest, Romania

Jon Roger Eidet,     Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Oslo, Norway

Diego Iacono

Departments of Neurology, Pathology, and Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

Neurodegenerative Clinic, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD, United States

Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

Juliann G. Kiang

Scientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

Fu-Cheng Lin

State Key Laboratory for Managing Biotic and Chemical Treats to the Quality and Safety of Agro-products, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang, China

State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, Zhejiang, China

Xiao-Hong Liu,     State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, Zhejiang, China

Lyubomyr Lytvynchuk,     Department of Ophthalmology, Justus-Liebig-University Giessen, Eye Clinic, University Hospital Giessen and Marburg GmbH, Giessen, Germany

Morten C. Moe

Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Oslo, Norway

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

Jan Motlik,     Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Science, Libechov, Czech Republic

Richárd Nagymihály,     Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Oslo, Norway

Yaroslav Nemesh,     Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Science, Libechov, Czech Republic

Goran Petrovski

Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Oslo, Norway

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

W. Bradley Rittase,     Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

Jason Sanders, MD ,     Chief Medical Officer, EV Biologics, Inc., Wyoming, United states

E. Marion Schneider,     Division of Experimental Anaesthesiology, University Hospital Ulm, Ulm, Germany;

Reed Selwyn,     Department of Radiology, University of New Mexico, Albuquerque, NM, United States

Huan-Bin Shi

State Key Laboratory for Managing Biotic and Chemical Treats to the Quality and Safety of Agro-products, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang, China

State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou, Zhejiang, China

Nicolae Suciu

Division of Obstetrics, Gynecology and Neonatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Department of Obstetrics and Gynecology, Polizu Clinical Hospital, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania

Dana Claudia Thompson,     Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, Bucharest, Romania

Silviu Cristian Voinea,     Department of Surgical Oncology, Prof. Dr. Alexandru Trestioreanu Oncology Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Erik F. Young,     Department of Electrical Engineering, Columbia University, New York, NY, United States

Yun-Ran Zhang,     State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, Zhejiang, China

Xue-Ming Zhu,     State Key Laboratory for Managing Biotic and Chemical Treats to the Quality and Safety of Agro-products, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang, China

Preface

Scope and objective

This book is a mutual effort of a group of authors with expertise in translational research and biotechnology. The book chapters discuss the concept of tissue barriers in conjunction with pathogenesis of diseases related to trauma, injury, and infection. To the subject, the authors present their view on structural and functional organization of barrier-forming tissues and the barrier-to-pathogen interactions as well as elucidate the emerging role of barrier-forming tissues in the regenerative medicine. On this account, the readers who are working on the development of new remedies for therapy of stress, injury, and degenerative diseases could avail themselves of in-depth understanding of the biology of tissue barriers, the mechanisms of biogenesis, and remodeling of tissue barriers and regulation of the barrier function under pathological conditions. Giving a wide-angle perspective on biomedical aspects of tissue barriers, this book is addressed to a broad audience of readers from students to practicing clinicians and experts in tissue barrier research.

The role of barrier-forming components and barrier functions in health and disease

From the research paradigm epistemology, a singularity of biological barrier represents a dividing surface or medium formed by biomolecules and cellular structures that separate an individual organism, i.e., "living matter, from surrounding nonliving matter and other organisms; and/or segregate systems and constituent parts within a living organism. Thus, the network of these barrier bio-interfaces provides compartmentalization of the organismal and cellular components, maintains their high degree of structural (i.e., low entropy) and functional organization, and controls flow of energy and information" in the form of biological cues under thermodynamically nonequilibrated conditions. In conjunction with the above, tissue barriers represent structural/functional entities formed by specialized, immunocompetent, or sentinel type of cells, which outline internal organs, tissues, tracts, and the entire body of organisms, are ubiquitously present in the parenchymal tissues and which sustain organismal immunochemical, metabolic, and thermal homeostasis. From an ontogeny perspective, tissue barriers are evolutionary evolved and adapted to: (i) maintain organismal morphogenesis, integrity, and endurance; (ii) regulate numerous vital physiological processes and thermal balance of organisms; as well as (iii) proactively and reactively respond to environmental impacts and damage; (iv) mediate interactions with other organisms; and (v) repel virus invasions.

The tissue barriers are configured and executed by ensembles of the barrier-forming cells of different histogenetic origins along with their extracellular matrices and intercellular junctions. In animals, these cells are, namely: mesenchymal, integument adipose, epithelial, endothelial, perivascular, immune, and ubiquitously distributed interstitial telocytes and reticuloendothelial cells. And in plants, the tissue barriers are constituted by epidermal, vascular, and sclerenchyma cells. It is broadly accepted that the structural-functional architecture of the barrier-forming networks is based on complex molecular and cellular mechanisms, including communications via cell-cell contacts, inter alia exchange with cell constituents, phagocytosis; and interactions of the above. Moreover, each of these cell the networks is subjected to modifications due flow of to the intrinsic morphogenetic stimuli, external forces, and impacts of diverse homeostatic cues (e.g., stress, danger) originated from tissue parenchyma and interstitial and circulating fluids. To this matter, the book chapters discuss several crucial aspects of the emerging signaling hubs mediated by telocytes and mesenchymal stromal cells in the histogenesis and integration of the barrier-forming tissues.

It ought to be noted that while the barrier-forming tissue systems are predominantly constituted by nonproliferating (e.g., terminally differentiated and G0-stage) cells, evidently, they are capable of self-rejuvenation and replacement of aberrant cells by both regulation of the tissue-specific progenitors and by recruitment of adult stem cells of mesenchymal and endothelial origins from milieux of stromal and lymphoid tissues and vascular niches. These pathways represent the basic cellular mechanisms, which mediate reconstitution and remodeling of the barrier integrity. Furthermore, these recruited cells sustain numerous housekeeping functions such as replenishing of impaired cells as well as phagocytosis of dead cells and their debris. In this light, it is worth to emphasize that a major population of nonprofessional phagocytic cells in stroma and vasculature is represented by endothelial and stromal fibroblastic cells. Therefore, it is hard to overstate the role of these cell lineages and their precursors in the responses to trauma and injury and in tissue regeneration. In this respect, the book chapters have also discussed the cellular mechanisms implicated in barrier functions mediated by endothelial and mesenchymal cells.

A remarkable plasticity attributed to the tissue barriers allows them to form numerous dynamic lines of defense to resist infections despite the pathogen's endeavor to subvert the host countermeasure mechanisms. This status quo is deranged in case of barrier breakdown due to an open wound or when acute or chronic diseases lead to impairment of barrier functions. The latter occur subsequently after ionizing irradiation that can damage the barrier-forming cells. Thus, exposure to gamma- or X-rays can trigger acute radiation sickness due to impairment and death of radiosensitive barrier-forming cells, namely, hematopoietic, lymphoid, mucosal epithelial, and vascular endothelial. Moreover, ionizing irradiation causes decline of the cell reproductive and regenerative capacity due to radiation-induced suppression of cell clonogenic potentials. Thus, the impact of irradiation and subsequent reactive responses can ultimately lead to delayed attrition of immune, intestinal, and vascular barriers accompanied by fluid loss, interstitial edema, and bacterial sepsis culminating in the failure of organs and systems. Advanced management of the radiation morbidity and mortality considers administration of diverse remedies. That includes bone marrow and stem cell transplant and application of related cell growth factors to restore the barrier function. In conjunction, recent developments in regenerative medicine and tissue engineering based on exploration of mesenchymal stromal cells brought a new perspective toward cell therapy of radiation injury. Indeed, firstly, populations of mesenchymal stromal cells represent a source of the adult stem cells [i.e., colony-forming unit fibroblasts, (CFU-F)] able to self-renew as well as to differentiate into multiple barrier-forming cell lineages. Secondly, numerous recent reports indicate that stromal fibroblasts and interstitial telocytes can also regulate functions of both parenchymal and barrier-forming tissues. These effects implicate diverse molecular mechanisms, including direct intercellular communication via homo- and heterocellular junctions, exchange with cellular constituents such as mitochondria, or by releasing regulatory cell factors within extracellular vesicles (e.g., exosomes). Moreover, a damaged tissue can promote migration of mesenchymal stromal cells (MSC) from the peripheral blood to the sites of injury, and stimulate their homing and release of factors sustaining aseptic environments and regeneration. These properties make MSCs and MSC-derived exosomes attractive for the cell therapy of diseases caused by radiation exposure, the radiation injury combined with secondary aggravating impacts such as trauma, and sepsis as well as for the acute viral infections. Recent developments in this area are also subjects of this book's discussion.

Perspectives and expectations from tissue barriers research

As our awareness of cellular mechanisms for tissue barrier regulation and reconstitution expands, so do the potential molecular targets for therapy of a variety of injuries and diseases. Then, it should always be remembered that an organism is prone to fail when barrier function fails. And, while separation of the effects due to the intrinsic cellular processes leading to the death of barrier-forming cells from the consequences of systemic hyperreactive responses is not a simple task, cell therapy that is focused on barrier-forming targets is likely to be broadly applicable in future approaches for injury treatment.

Nikolai V Gorbunov, PhD

Chapter One: Roles and distribution of telocytes in tissue organization in health and disease

Carmen Elena Condrat ¹ , a , Mădălina Gabriela Barbu ¹ , a , Dana Claudia Thompson ¹ , a , Cezara Alina Dănilă ¹ , Andreea Elena Boboc ¹ , Nicolae Suciu ² , ³ , Dragoș Crețoiu ¹ , ⁴ , and Silviu Cristian Voinea ⁵       ¹ Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, Bucharest, Romania      ² Division of Obstetrics, Gynecology and Neonatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania      ³ Department of Obstetrics and Gynecology, Polizu Clinical Hospital, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania      ⁴ Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania      ⁵ Department of Surgical Oncology, Prof. Dr. Alexandru Trestioreanu Oncology Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Abstract

Telocytes (TCs) are interstitial cells that distinguish themselves through their particular architecture, consisting of a relatively small cell body that emits remarkably long and narrow prolongations called telopodes (Tps). Previously known as interstitial Cajal-like cells, TCs manage to develop complex networks in almost all organs of the human body. Although staining positively for vimentin antibody, some uncertainty still persists over the mesenchymal origin of these cells. The election method for the precise detection of biological structures is focused ion beam scanning electron microscopy, which ensures an accurate visualization of cellular architecture by providing sharper images of three-dimensional bodies, reaching nanoscale resolution. This approach has thus become the gold-standard for the identification of TCs. With the aid of currently available technology, TCs have been demonstrated to cover a wide range of functions that stretches from their role in electrical conduction and contractility adjustment to the coordination of tissue regeneration and angiogenesis. Because of their ability to form homo- and/or heterojunctions, TCs successfully provide resistant mechanical support. They exert their roles by ensuring intercellular signaling, either through direct cell–cell interaction or through juxtacrine and/or paracrine interactions aided by shedding bodies and exosomes delivered by Tps. The complex networks regulated by TCs have recently been proposed to form barriers between parenchymal compartments. This theory is supported by the abundant collagen fibrils that surround the Tps, thus strengthening their pivotal role in the establishment of tissue architecture. The numerous demonstrated and potential roles of TCs without a doubt require further investigation, especially because of their promising functions in regenerative medicine.

Keywords

Cell signaling; Disease; Telocytes; Tissue barrier; Tissue homeostasis

1. Introduction

Host tissue barriers arrange numerous external and internal interfaces evolutionary adapted to sustain morphogenesis, cellular and molecular integrity, metabolic homeostasis and