Current Topics in and

Volume 430

Series Editors Rafi Ahmed School of Medicine, Rollins Research Center, Emory University, Atlanta, GA, USA Shizuo Akira Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan Klaus Aktories Faculty of Medicine, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Freiburg, Baden-Württemberg, Germany Arturo Casadevall W. Harry Feinstone Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Richard W. Compans Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA Jorge E. Galan Boyer Ctr. for Molecular Medicine, School of Medicine, Yale University, New Haven, CT, USA Adolfo Garcia-Sastre Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA Bernard Malissen Parc Scientifique de Luminy, Centre d’Immunologie de Marseille-Luminy, Marseille, France Rino Rappuoli GSK , , The review series Current Topics in Microbiology and Immunology provides a synthesis of the latest research findings in the areas of molecular immunology, bacteriology and virology. Each timely volume contains a wealth of information on the featured subject. This review series is designed to provide access to up-to-date, often previously unpublished information. 2019 Impact Factor: 3.095., 5-Year Impact Factor: 3.895 2019 Eigenfaktor Score: 0.00081, Article Influence Score: 1.363 2019 Cite Score: 6.0, SNIP: 1.023, h5-Index: 43

More information about this series at http://www.springer.com/series/82 Fabio Bagnoli • Rino Rappuoli Editors

Three Dimensional Human Organotypic Models for Biomedical Research

Responsible series editor: Rino Rappuoli

123 Editors Fabio Bagnoli Rino Rappuoli GSK Vaccines Research GSK Vaccines Research Siena, Italy Siena, Italy

ISSN 0070-217X ISSN 2196-9965 (electronic) Current Topics in Microbiology and Immunology ISBN 978-3-030-62451-4 ISBN 978-3-030-62452-1 (eBook) https://doi.org/10.1007/978-3-030-62452-1

© Springer Nature Switzerland AG 2021 Chapters ‘Progress on Reconstructed Human Skin Models for Allergy Research and Identifying Contact Sensitizers’ and ‘Human Organotypic Models for Anti-infective Research’ are licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/ 4.0/). For further details see license information in the chapters. This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publi- cation does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface

Animal models are currently extensively used for studying host-pathogen interac- tions, mechanism of action and efficacy of vaccines and drugs, cancer formation, as well as for deciphering the pathogenesis of many human diseases. On the basis of such studies many invaluable discoveries have been done and new medical inter- ventions developed. However, animal models have several limitations that can significantly affect their reliability for translating the observations to humans. Indeed, besides the many examples of successful outcome of research performed using animal models, unfortunately there are also notable cases of failure. Furthermore, genome and immunology studies recently performed by several research teams such as the one led by Mark Davis, are showing differences between humans and mice that explain limitations of mouse models in predicting clinical outcomes and stress the need of performing research on human samples. Therefore, models that can better reproduce human tissues are urgently needed. Three dimensional organotypic human models are informative and tractable experimental systems and they represent a valid alternative to animal models. Efforts aimed at establishing such models is receiving a lot of attention from most areas of biomedical research and many human tissues can today be cultivated in vitro and used for several research objectives. Examples of such models include reconstruction of human epithelia (skin, intestine, stomach, lung) from cells culti- vated in culture. The key element of these models are the epithelial cells, but other cell types (e.g., immune cells) can be added. To accomplish this goal researchers are using cutting-edge technologies such as induced pluripotent stem cells, which can be used to generate virtually any sort of cell including macrophages and neutrophils. These models are amenable for the dissecting the role of particular cell types in a certain phenomenon. A different approach relies on the use of tissue explants obtained from donors undergoing surgery operations. Certain explants can be kept in culture for quite a long time allowing many kinds of experiments. They contain all the resident cells of the tissue and they can reflect quite closely certain processes that happen in the patients. Although most of these models still have the important limitation of lacking blood circulation, they certainly represent an important step forward for biomedical research and combined with powerful

v vi Preface analytical tools such as RT-PCR, DNA-microarrays, confocal and two-photon microscopy as well as quantitative and in situ mass spectrometry they are able to shed light on many yet unknown physiological, immunological and pathological mechanisms. Observations done using these models can complement and some- times replace animal models allowing to reduce the number of animals used in experimental research, which is another very important achievement. This book attempts to provide a general overview, including detailed scientific and technical aspects, of on a nascent but already very active and fruitful area of research. It covers major areas of biomedical research conducted using these models such as infectious diseases, cancer, allergic diseases as well as drug/ discovery and toxicology studies. It provides an unprecedented overview of recent developments and knowledge on very diverse human organotypic models and their applications. We hope it will help many basic scientists, physicians and applied scientists in designing their next experiments for understanding pathological or medicinal mechanisms and better predict the same phenomena in patients.

Conflict of Interest

Rino Rappuoli and Fabio Bagnoli are employees of the GSK group of companies. RR and FB hold shares in the GSK group of companies. FB holds pending and issued patents on S. aureus vaccine formulations.

Siena, Italy Fabio Bagnoli Rino Rappuoli Contents

Part I Three Dimensional Human Organotypic Models for Studying Infectious Diseases Human Three-Dimensional Models for Studying Skin Pathogens...... 3 Elena Boero, Malgorzata Ewa Mnich, Andrea Guido Oreste Manetti, Elisabetta Soldaini, Luca Grimaldi and Fabio Bagnoli Human Organotypic Respiratory Models ...... 29 Mattias Svensson and Puran Chen Human Gastrointestinal Organoid Models for Studying Microbial Disease and Cancer ...... 55 Jayati Chakrabarti, Martha B. Dua-Awereh, Loryn Holokai and Yana Zavros Human Organotypic Models for Anti-infective Research ...... 77 Astrid Hendriks, Ana Rita Cruz, Elisabetta Soldaini, Andrea Guido Oreste Manetti and Fabio Bagnoli

Part II Three Dimensional Human Organotypic Models for Studying Non-infectious Diseases Progress on Reconstructed Human Skin Models for Allergy Research and Identifying Contact Sensitizers ...... 103 Charlotte Rodrigues Neves and Susan Gibbs Cancer Explant Models ...... 131 Christian T. Stackhouse, George Yancey Gillespie and Christopher D. Willey Organotypic Models of Lung Cancer ...... 161 Anna Pomerenke

vii viii Contents

Pancreatic Cancer Organotypic Models ...... 183 Abigail Coetzee, Richard Grose and Hemant Kocher Breast Organotypic Cancer Models ...... 199 Pilar Carranza-Rosales, Nancy Elena Guzmán-Delgado, Irma Edith Carranza-Torres, Ezequiel Viveros-Valdez and Javier Morán-Martínez Preclinical Organotypic Models for the Assessment of Novel Cancer Therapeutics and Treatment ...... 225 Carol Ward, James Meehan, Mark Gray, Ian H. Kunkler, Simon P. Langdon, Alan Murray and David Argyle Overview and Comparison of Intestinal Organotypic Models, Intestinal Cells, and Intestinal Explants Used for Toxicity Studies ...... 247 Marc Maresca, Philippe Pinton, El Hassan Ajandouz, Sandrine Menard, Laurent Ferrier and Isabelle P. Oswald Correction to: Human Organotypic Models for Anti-infective Research ...... 265 Astrid Hendriks, Ana Rita Cruz, Elisabetta Soldaini, Andrea Guido Oreste Manetti and Fabio Bagnoli