Wang Hongjun, Ciccocioppo Rachele, Terai Shuji, Shoeibi Sara, Carnevale Gianluca, De Marchi Giulia, Tsuchiya Atsunori, Ishii Soichi, Tonouchi Takafumi, Furuyama Kaito, Yang Yuan, Mito Masaki, Abe Hiroyuki, Di Tinco Rosanna, Cardinale Vincenzo
Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA; Ralph H Johnson Veteran Medical Center, Charleston, South Carolina, USA.
Department of Medicine, Gastroenterology Unit, Pancreas Institute, A.O.U.I. Policlinico G.B. Rossi & University of Verona, Verona, Italy.
Cytotherapy. 2025 Mar;27(3):259-278. doi: 10.1016/j.jcyt.2024.11.008. Epub 2024 Nov 19.
Cellular and gene therapy (CGT) products have emerged as a popular approach in regenerative medicine, showing promise in treating various pancreatic and liver diseases in numerous clinical trials. Before these therapies can be tested in human clinical trials, it is essential to evaluate their safety and efficacy in relevant animal models. Such preclinical testing is often required to obtain regulatory approval for investigational new drugs. However, there is a lack of detailed guidance on selecting appropriate animal models for CGT therapies targeting specific pancreatic and liver conditions, such as pancreatitis and chronic liver diseases. In this review, the gastrointestinal committee for the International Society for Cell and Gene Therapy provides a summary of current recommendations for animal species and disease model selection, as outlined by the US Food and Drug Administration, with references to EU EMA and Japan PMDA. We discuss a range of small and large animal models, as well as humanized models, that are suitable for preclinical testing of CGT products aimed at treating pancreatic and liver diseases. For each model, we cover the associated pathophysiology, commonly used metrics for assessing disease status, the pros and limitations of the models, and the relevance of these models to human conditions. We also summarize the use and application of humanized mouse and other animal models in evaluating the safety and efficacy of CGT products. This review aims to provide comprehensive guidance for selecting appropriate animal species and models to help bridge the gap between the preclinical research and clinical trials using CGT therapies for specific pancreatic and liver diseases.
细胞和基因治疗（CGT）产品已成为再生医学中一种流行的方法，在众多临床试验中显示出治疗各种胰腺和肝脏疾病的潜力。在这些疗法能够在人体临床试验中进行测试之前，在相关动物模型中评估其安全性和有效性至关重要。通常需要进行此类临床前测试以获得研究性新药的监管批准。然而，对于针对特定胰腺和肝脏疾病（如胰腺炎和慢性肝病）的CGT疗法，缺乏关于选择合适动物模型的详细指导。在本综述中，国际细胞和基因治疗协会胃肠委员会总结了美国食品药品监督管理局概述的当前关于动物物种和疾病模型选择的建议，并参考了欧盟药品管理局和日本药品和医疗器械管理局的相关内容。我们讨论了一系列适用于针对胰腺和肝脏疾病的CGT产品临床前测试的小型和大型动物模型以及人源化模型。对于每个模型，我们涵盖了相关的病理生理学、评估疾病状态常用的指标、模型的优缺点以及这些模型与人类疾病的相关性。我们还总结了人源化小鼠和其他动物模型在评估CGT产品安全性和有效性方面的使用和应用。本综述旨在为选择合适的动物物种和模型提供全面指导，以帮助弥合针对特定胰腺和肝脏疾病使用CGT疗法进行临床前研究与临床试验之间的差距。
