Brandhorst Daniel, Brandhorst Heide, Johnson Paul R V
Nuffield Department of Surgical Sciences, University of Oxford, United Kingdom.
Rev Diabet Stud. 2017 Spring;14(1):22-38. doi: 10.1900/RDS.2017.14.22. Epub 2017 Jun 12.
In comparison to procedures used for the separation of individual cell types from other organs, the process of human pancreatic islet isolation aims to digest the pancreatic exocrine matrix completely without dispersing the individual cells within the endocrine cell cluster. This objective is unique within the field of tissue separation, and outlines the challenge of islet isolation to balance two opposing priorities. Although significant progress has been made in the characterization and production of enzyme blends for islet isolation, there are still numerous areas which require improvement. The ultimate goal of enzyme production, namely the routine production of a consistent and standardized enzyme blend, has still not been realized. This seems to be mainly the result of a lack of detailed knowledge regarding the structure of the pancreatic extracellular matrix and the synergistic interplay between collagenase and different supplementary proteases during the degradation of the extracellular matrix. Furthermore, the activation of intrinsic proteolytic enzymes produced by the pancreatic acinar cells, also impacts on the chance of a successful outcome of human islet isolation. This overview discusses the challenges of pancreatic enzymatic digestion during human islet isolation, and outlines the developments in this field over the past 5 decades.
与从其他器官分离单个细胞类型所使用的程序相比，人类胰岛分离过程旨在完全消化胰腺外分泌基质，而不分散内分泌细胞簇中的单个细胞。这一目标在组织分离领域是独一无二的，它勾勒出胰岛分离的挑战，即要平衡两个相互对立的优先事项。尽管在用于胰岛分离的酶混合物的表征和生产方面已经取得了重大进展，但仍有许多领域需要改进。酶生产的最终目标，即常规生产一致且标准化的酶混合物，尚未实现。这似乎主要是由于缺乏关于胰腺细胞外基质结构以及在细胞外基质降解过程中胶原酶与不同补充蛋白酶之间协同相互作用的详细知识。此外，胰腺腺泡细胞产生的内源性蛋白水解酶的激活，也会影响人类胰岛分离成功的几率。本综述讨论了人类胰岛分离过程中胰腺酶消化的挑战，并概述了过去50年该领域的发展情况。
