Isolation of Pancreatic Islets from Nonhuman Primates

Isolation of Pancreatic Islets from Nonhuman Primates
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DOI:
10.1007/978-3-319-39824-2_5
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发表时间:
2016-01-01
期刊:
PANCREATIC ISLET ISOLATION: FROM THE MOUSE TO THE CLINIC
影响因子:
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通讯作者:
Berman, Dora M.
Berman, Dora M.
中科院分区:
其他
文献类型:
--
作者:
Berman, Dora M.

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非人灵长类动物(NHP)是开发β细胞替代策略的高度相关的临床前动物模型。NHP和人类之间密切的系统发育和免疫学关系导致各种生物制剂与NHP细胞的交叉反应性,以及人类和NHP胰岛之间非常相似的细胞结构,这与在啮齿动物胰岛中观察到的明显不同。人类或NHP胰岛中内分泌细胞的组成和位置随机分布并与血管相关,具有功能影响和旁分泌相互作用的倾向。此外,将在啮齿类动物模型中证明成功的方法转化为临床方法是有限的。因此,从NHP研究中收集的数据可以构成向FDA提交IND的基础。本章详细描述了从NHP中分离胰岛的关键方面,从器官获取到胰岛功能评估,比较并强调了人类和NHP胰岛分离程序之间的相似性。
Nonhuman primates (NHP) constitute a highly relevant pre-clinical animal model to develop strategies for beta cell replacement. The close phylogenetic and immunologic relationship between NHP and humans results in cross-reactivity of various biological agents with NHP cells, as well as a very similar cytoarchitecture between islets from human and NHP that is strikingly different from that observed in rodent islets. The composition and location of endocrine cells in human or NHP islets, randomly distributed and associated with blood vessels, have functional consequences and a predisposition for paracrine interactions. Furthermore, translation of approaches that proved successful in rodent models to the clinic has been limited. Consequently, data collected from NHP studies can form the basis for an IND submission to the FDA. This chapter describes in detail the key aspects for isolation of islets from NHP, from organ procurement up to assessment of islet function, comparing and emphasizing the similarities between isolation procedures for human and NHP islets.