Therapeutic and Diagnostic Guidelines
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2021; 12(4): 306-330
Published online Apr 15, 2021. doi: 10.4239/wjd.v12.i4.306
Feasibility of large experimental animal models in testing novel therapeutic strategies for diabetes
Masaki Nagaya, Koki Hasegawa, Ayuko Uchikura, Kazuaki Nakano, Masahito Watanabe, Kazuhiro Umeyama, Hitomi Matsunari, Kenji Osafune, Eiji Kobayashi, Hiromitsu Nakauchi, Hiroshi Nagashima
Masaki Nagaya, Kazuaki Nakano, Masahito Watanabe, Kazuhiro Umeyama, Hitomi Matsunari, Hiroshi Nagashima, Meiji University International Institute for Bio-Resource Research, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
Masaki Nagaya, Department of Immunology, St. Marianna University School of Medicine, Kawasaki 261-8511, Kanagawa, Japan
Koki Hasegawa, Ayuko Uchikura, Kazuaki Nakano, Masahito Watanabe, Kazuhiro Umeyama, Hitomi Matsunari, Hiroshi Nagashima, Laboratory of Medical Bioengineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
Kazuaki Nakano, Masahito Watanabe, Kazuhiro Umeyama, Research and Development, PorMedTec Co. Ltd, Kawasaki 214-0034, Kanagawa, Japan
Kenji Osafune, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Kyoto, Japan
Eiji Kobayashi, Department of Organ Fabrication, Keio University School of Medicine, Shinjuku 160-8582, Tokyo, Japan
Hiromitsu Nakauchi, Institute for Stem Cell Biology and Regenerative Medicine, Department of Genetics, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, United States
Hiromitsu Nakauchi, Division of Stem Cell Therapy, Institute of Medical Science, The University of Tokyo, Minato 108-8639, Tokyo, Japan
Author contributions: Nagaya M and Nagashima H contributed conception and design, financial support, collection and assembly of data, data analysis, and interpretation, manuscript writing, and final approval of the manuscript; Hasegawa K, Uchikura A, Nakano K, Watanabe M, Umeyama K and Matsunari H contributed collection and assembly of data, data analysis and interpretation; Osafune K, Kobayashi E and Nakauchi N contributed data analysis, and interpretation.
Conflict-of-interest statement: The authors has nothing to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Masaki Nagaya, MD, PhD, Professor, Meiji University International Institute for Bio-Resource Research, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki 214-8571, Kanagawa, Japan. m2nagaya@gmail.com
Received: January 9, 2021
Peer-review started: January 9, 2021
First decision: January 24, 2021
Revised: January 30, 2021
Accepted: March 11, 2021
Article in press: March 11, 2021
Published online: April 15, 2021
Processing time: 89 Days and 20.3 Hours
Abstract

Diabetes is among the top 10 causes of death in adults and caused approximately four million deaths worldwide in 2017. The incidence and prevalence of diabetes is predicted to increase. To alleviate this potentially severe situation, safer and more effective therapeutics are urgently required. Mice have long been the mainstay as preclinical models for basic research on diabetes, although they are not ideally suited for translating basic knowledge into clinical applications. To validate and optimize novel therapeutics for safe application in humans, an appropriate large animal model is needed. Large animals, especially pigs, are well suited for biomedical research and share many similarities with humans, including body size, anatomical features, physiology, and pathophysiology. Moreover, pigs already play an important role in translational studies, including clinical trials for xenotransplantation. Progress in genetic engineering over the past few decades has facilitated the development of transgenic animals, including porcine models of diabetes. This article discusses features that attest to the attractiveness of genetically modified porcine models of diabetes for testing novel treatment strategies using recent technical advances.

Keywords: Pancreatic islet; Diabetes mellitus; Pig; Transgenic; Genetic engineering; Transplantation; Xenotransplantation

Core Tip: Safer and more effective therapeutics are urgently required for managing the diabetes epidemic. Mice have been used predominantly as preclinical models for basic research on diabetes, although murine models are not ideally suited for translating basic knowledge into clinical applications. This article discusses features that attest to the attractiveness of genetically modified porcine models of diabetes for testing novel treatment strategies using recent technical advances.