Humanized Mouse Models for Type 1 Diabetes Including Pancreatic Islet Transplantation

Humanized Mouse Models for Type 1 Diabetes Including Pancreatic Islet Transplantation
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DOI:
10.1055/s-0034-1390446
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发表时间:
2015-01-01
影响因子:
2.2
通讯作者:
Waskow, C.
Waskow, C.
中科院分区:
医学4区
文献类型:
--
作者:
Rahmig, S.;Bornstein, S. R.;Waskow, C.

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我们在这里评论现有的小鼠模型对1型糖尿病研究的适用性,包括治疗性胰岛移植的研究。主要重点将放在需要最小侵入性程序的模型上。大多数生物过程太复杂,不能在试管中完全概括。先天甚至获得性免疫反应的研究涉及许多不同的细胞类型和器官,这使得体外研究不可靠,但也为替代模式生物的使用提供了极端的挑战。由于伦理和技术的限制,直接在人体内研究这些过程是不可能的。为了解决这一问题,小鼠或大鼠等小动物模型经常被用来研究复杂疾病的机制。这带来了对包括1型糖尿病(T1D)在内的造血和免疫细胞功能的许多洞察;然而,6500万年的进化引入了老鼠和人类之间的显著差异1。事实上,许多基于老鼠2 3的研究提出的治疗方法承诺预防甚至逆转T1D,但没有一种进入临床。原因是啮齿类动物和人类在免疫系统和β细胞方面存在主要的物种特异性差异。
We comment here on the suitability of available mouse models for type 1 diabetes research including research on therapeutic pancreatic islet transplantation. The major emphasis will be laid on models that require minimal invasive procedures. Most biological processes are too complex for a complete recapitulation in a test tube. The study of innate or even adaptive immune responses involves a number of different cell types and organs making in vitro studies unreliable but also providing extreme challenges for the use of surrogate model organisms. Studying these processes directly in humans is impossible due to ethical and technical constraints. To resolve this problem small animal models such as mice or rats are frequently used to study mechanisms of complex diseases. This has brought much insight into hematopoiesis and immune cell function including type 1 diabetes (T1D); however, 65 million years of evolution introduced striking differences between mice and humans 1. In fact, none of the many suggested therapies arising from studies using mice 2 3 that have promised prevention or even reversion of T1D made it into the clinic yet 4 5 6. The reason for this are major species-specific differences between rodents and humans regarding the immune system and beta cells.