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Advances in Experimental Medicine and Biology Volume 938 Editorial Board IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel N.S. ABEL LAJTHA, Kline Institute for Psychiatric Research, Orangeburg, NY, USA JOHN D. LAMBRIS, University of Pennsylvania, Philadelphia, PA, USA RODOLFO PAOLETTI, University of Milan, Milan, Italy

More information about this series at http://www.springer.com/series/5584

Miriam Ramírez-Domínguez Editor Pancreatic Islet Isolation From the Mouse to the Clinic

Editor Miriam Ramírez-Domínguez Laboratory of Cell Therapy of Diabetes, Department of Pediatrics, Faculty of Medicine and Odontology, Hospital Cruces University of the Basque Country (UPV/EHU) Leioa, Biscay, Spain ISSN 0065-2598 ISSN 2214-8019 (electronic) Advances in Experimental Medicine and Biology ISBN 978-3-319-39822-8 ISBN 978-3-319-39824-2 (ebook) DOI 10.1007/978-3-319-39824-2 Library of Congress Control Number: 2016948757 Springer International Publishing Switzerland 2016 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 publication 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, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland

I dedicate this book to my family, for their unconditional love and support.

Preface Pancreatic islets contain the beta cells, which are the source of insulin in the body, and hence, in terms of diabetes, they are fundamental structures for any preclinical in vitro or in vivo studies in animal models or related to human transplantation. However, human and animal islet isolation has been described as the work of a craftsman as it is a delicate process that is affected by many variables, requiring the acquisition of specific and specialist know-how. While islet isolation procedures are similar in both animal models and humans, the islets from different species have distinct anatomical and functional characteristics. Therefore, both common and unique features between species must be taken into account when isolating these structures in order to: (1) avoid inconsistencies introduced by the procedure used for islet isolation ; (2) optimize the conditions of the isolation procedure and its outcome in terms of islet quality, as well as the time and cost of isolation; and (3) facilitate the translation of procedures developed in animal models to clinical settings. This book, aimed at experts and beginners, addresses the challenges, pitfalls, and particularities of clinical islet isolation and those associated with their isolation from model animals. The book reviews the state of the art in this field, assessing the similarities and differences between human and animal islets, and how these influence their isolation, enabling strategies to be devised that can be translated to the clinic. The first chapter is an introduction to the historical background of islet isolation, a fascinating story that has progressed hand in hand with that of islet transplantation. Indeed, our current mastery of both these processes can be expected to pave the way for the development of future cell therapies that will address the shortage of donor islets to treat diabetes. In the following chapters, the procedures to isolate islets from mice, pigs, and nonhuman primates are reviewed, the main animal models used in preclinical studies and translational approaches. Working with mice has many advantages (they are relatively economic to maintain and easy to work with, they reproduce rapidly and in suitable numbers, etc.), and this species represents a true workhorse in this field of research. Porcine islets represent a very interesting model system, providing raw material for xenotransplantation, while nonhuman primates are the closest phylogenetic animal model to humans, the two species sharing a similar islet cytoarchitecture. As such, data obtained in nonhuman primates has a strong translational potential. vii

viii Preface The lasts chapters focus on clinical islet isolation and all the processes and facilities required to establish a Clinical Islet Program: the donor organ, the effect of BMI, cold ischemia time, pancreas preservation, the procedure of islet isolation, islet culture, etc. Finally, I would like to express my gratitude to all the authors who have contributed to this book and for the time and effort they dedicated to make it possible. I feel especially indebted to Dr. Juan Domínguez-Bendala for his assistance and his constant support. In addition, I would also like to thank Meran Owen and Tanja Koppejan at Springer for their invaluable assistance during the preparation of the book. Leioa, Biscay, Spain Miriam Ramírez-Domínguez

Contents 1 Historical Background of Pancreatic Islet Isolation... 1 Miriam Ramírez-Domínguez 2 The Different Faces of the Pancreatic Islet... 11 Midhat H. Abdulreda, Rayner Rodriguez-Diaz, Over Cabrera, Alejandro Caicedo, and Per-Olof Berggren 3 Isolation of Mouse Pancreatic Islets of Langerhans... 25 Miriam Ramírez-Domínguez 4 Pancreatic Islets: Methods for Isolation and Purification of Juvenile and Adult Pig Islets... 35 Heide Brandhorst, Paul R.V. Johnson, and Daniel Brandhorst 5 Isolation of Pancreatic Islets from Nonhuman Primates... 57 Dora M. Berman 6 Necessities for a Clinical Islet Program... 67 Wayne J. Hawthorne 7 Clinical Islet Isolation... 89 Wayne J. Hawthorne, Lindy Williams, and Yi Vee Chew Index... 123 ix

Contributors Midhat H. Abdulreda Diabetes Research Institute/Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA Per-Olof Berggren Diabetes Research Institute/Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet Karolinska University Hospital L1, Stockholm, Sweden Dora M. Berman Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA Daniel Brandhorst Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK Heide Brandhorst Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK Over Cabrera Diabetes Research Institute/Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA Alejandro Caicedo Diabetes Research Institute/Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA Yi Vee Chew National Pancreas and Islet Transplant Laboratories, The Westmead Institute for Medical Research, Westmead, NSW, Australia Wayne J. Hawthorne National Pancreas and Islet Transplant Laboratories, The Westmead Institute for Medical Research, Westmead, NSW, Australia Department of Surgery, Westmead Clinical School, Westmead Hospital, University of Sydney, Westmead, NSW, Australia xi

xii Contributors Paul R.V. Johnson Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK Oxford NIHR Biomedical Research Centre, Oxford, UK Miriam Ramírez-Domínguez Laboratory of Cell Therapy of Diabetes, Department of Pediatrics, Faculty of Medicine and Odontology, Hospital Cruces, University of the Basque Country (UPV/EHU), Leioa, Biscay, Spain Rayner Rodriguez-Diaz Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden Lindy Williams National Pancreas and Islet Transplant Laboratories, The Westmead Institute for Medical Research, Westmead, NSW, Australia