Concise Review: Humanized Models of Tumor Immunology in the 21st Century: Convergence of Cancer Research and Tissue Engineering
Concise Review: Humanized Models of Tumor Immunology in the 21st Century: Convergence of Cancer Research and Tissue Engineering
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DOI：
10.1002/stem.1978
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发表时间：
2015-06-01
期刊：
影响因子：
5.2
通讯作者：
Hutmacher, Dietmar Werner
中科院分区：
文献类型：
--
作者：
Holzapfel, Boris Michael;Wagner, Ferdinand;Hutmacher, Dietmar Werner
尽管在动物研究中得到了积极的测试，但超过80%的新型候选药物在人体测试时未能证明其疗效。这主要是由于使用了临床前模型，这些模型不能概括人类的生理或病理过程。因此，转化医学领域的关键挑战之一是使模式生物小鼠更人性化。为了获得人类医学预后问题的答案，可以改变小鼠的基因组，以创造一个更宽容的宿主，允许人类细胞系统的植入。过去已经证明，这些策略可以提高我们对肿瘤免疫学的理解。然而，这些平台的转化效益仍有待证明。在21世纪的世纪，世界各地的一些研究小组和财团接受了挑战，以提高我们对如何使动物的遗传密码，细胞，以及基于组织工程原理，其细胞外微环境，其组织或整个器官人性化的理解，最终目标是促进新的治疗策略从实验室到床边的翻译。本文概述了肿瘤免疫学的人源化模型的最新发展，并强调了该领域的未来发展，如组织工程和再生医学策略的应用，以进一步增强人源化小鼠模型系统。干细胞2015;33：1696-1704
Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to make the model organism mouse more human. To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems. Stem Cells2015;33:1696-1704