Dehoux Jean-Paul, Gianello Pierre
Universite catholique de Louvain, Faculty of Medicine, Experimental Surgery Unit, Brussels, Belgium.
Front Biosci. 2007 Sep 1;12:4864-80. doi: 10.2741/2434.
Animal models have been extensively used in transplantation research. However, animal experimentation is contentious and subject to legal and ethical restrictions. Most experiments are carried out on rodents, but crucial prerequisites for the development of safe pre-clinical protocols in biomedical research are needed through suitable large animal models. In transplantation particularly, large animal models have developed dramatically. This article provides an overview of the large animal models commonly used to evaluate organ transplant experiments and analyzes the specificity of several models in various situations such as induction of allospecific tolerance and xenotransplantation. The key determination that remains be addressed is the most appropriate species and strains to model human immune and physiological systems. Because of their phylogenetic and physiologic similarities to man, non-human primates play an increasingly important role in pre-clinical testing. Nevertheless, a number of studies have shown the pig to be a reliable large animal model for transplantation research, and the availability of genetically defined or modified pigs establishes a stronger position for pigs as a large animal model.
动物模型已广泛应用于移植研究。然而,动物实验存在争议,并受到法律和伦理限制。大多数实验是在啮齿动物身上进行的,但生物医学研究中安全的临床前方案的开发需要通过合适的大型动物模型来实现关键的先决条件。特别是在移植领域,大型动物模型有了显著发展。本文概述了常用于评估器官移植实验的大型动物模型,并分析了几种模型在同种异体特异性耐受诱导和异种移植等各种情况下的特异性。仍有待解决的关键决定因素是模拟人类免疫和生理系统的最合适物种和品系。由于与人类在系统发育和生理上的相似性,非人灵长类动物在临床前测试中发挥着越来越重要的作用。尽管如此,一些研究表明猪是移植研究中可靠的大型动物模型,基因定义或修饰猪的可用性为猪作为大型动物模型奠定了更有利的地位。