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胰岛素分泌β细胞的 3D 模型:从原代胰岛细胞到干细胞衍生胰岛。

3D-Models of Insulin-Producing β-Cells: from Primary Islet Cells to Stem Cell-Derived Islets.

机构信息

Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.

Department of Biology and Bioengineering, Chalmers University of Technology, Gothenburg, Sweden.

出版信息

Stem Cell Rev Rep. 2018 Apr;14(2):177-188. doi: 10.1007/s12015-017-9783-8.

DOI:10.1007/s12015-017-9783-8
PMID:29181780
Abstract

There is a need for physiologically relevant assay platforms to provide functionally relevant models of diabetes, to accelerate the discovery of new treatment options and boost developments in drug discovery. In this review, we compare several 3D-strategies that have been used to increase the functional relevance of ex vivo human primary pancreatic islets and developments into the generation of stem cell derived pancreatic beta-cells (β-cells). Special attention will be given to recent approaches combining the use of extracellular matrix (ECM) scaffolds with pancreatic molecular memory, which can be used to improve yield and functionality of in vitro stem cell-derived pancreatic models. The ultimate goal is to develop scalable cell-based platforms for diabetes research and drug screening. This article will critically assess key aspects related to in vitro pancreatic 3D-ECM models and highlight the most promising approaches for future research.

摘要

需要有生理相关的检测平台来提供更具功能相关性的糖尿病模型,以加速新的治疗方案的发现并推动药物研发的进展。在这篇综述中,我们比较了几种 3D 策略,这些策略被用于提高体外人原代胰腺胰岛的功能相关性,并发展为干细胞衍生的胰腺β细胞(β细胞)。特别关注的是最近将细胞外基质(ECM)支架与胰腺分子记忆结合使用的方法,这可用于提高体外干细胞衍生的胰腺模型的产量和功能。最终目标是开发用于糖尿病研究和药物筛选的可扩展的基于细胞的平台。本文将批判性地评估与体外胰腺 3D-ECM 模型相关的关键方面,并强调未来研究中最有前途的方法。

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3D-Models of Insulin-Producing β-Cells: from Primary Islet Cells to Stem Cell-Derived Islets.胰岛素分泌β细胞的 3D 模型:从原代胰岛细胞到干细胞衍生胰岛。
Stem Cell Rev Rep. 2018 Apr;14(2):177-188. doi: 10.1007/s12015-017-9783-8.
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Stem Cells as a Source of Pancreatic Cells for Production of 3D Bioprinted Bionic Pancreas in the Treatment of Type 1 Diabetes.干细胞作为产生用于治疗 1 型糖尿病的 3D 生物打印仿生胰腺的胰腺细胞的来源。
Cells. 2021 Jun 18;10(6):1544. doi: 10.3390/cells10061544.
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Building Biomimetic Potency Tests for Islet Transplantation.

本文引用的文献

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A macroporous heparin-releasing silk fibroin scaffold improves islet transplantation outcome by promoting islet revascularisation and survival.一种大孔肝素释放丝素蛋白支架通过促进胰岛血管再生和存活来改善胰岛移植结果。
Acta Biomater. 2017 Sep 1;59:210-220. doi: 10.1016/j.actbio.2017.06.039. Epub 2017 Jun 27.
2
A bilaminated decellularized scaffold for islet transplantation: Structure, properties and functions in diabetic mice.用于胰岛移植的双层脱细胞支架:结构、特性和在糖尿病小鼠中的功能。
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Micro-fabricated scaffolds lead to efficient remission of diabetes in mice.
构建胰岛移植的仿生功效测试。
Diabetes. 2021 Feb;70(2):347-363. doi: 10.2337/db20-0297.
4
Insulin/Glucose-Responsive Cells Derived from Induced Pluripotent Stem Cells: Disease Modeling and Treatment of Diabetes.诱导多能干细胞衍生的胰岛素/葡萄糖反应细胞:糖尿病的疾病建模和治疗。
Cells. 2020 Nov 12;9(11):2465. doi: 10.3390/cells9112465.
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Human Melanocyte-Derived Spheroids: A Precise Test System for Drug Screening and a Multicellular Unit for Tissue Engineering.人黑素细胞来源的球体:用于药物筛选的精确测试系统和组织工程的多细胞单元。
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Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction.塑造胰腺 β 细胞的分化和功能:力学转导的影响。
Cells. 2020 Feb 11;9(2):413. doi: 10.3390/cells9020413.
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Extracellular matrix and the maintenance and loss of peripheral immune tolerance in autoimmune insulitis.细胞外基质与自身免疫性胰岛炎中外周免疫耐受的维持和丧失。
Curr Opin Immunol. 2018 Dec;55:22-30. doi: 10.1016/j.coi.2018.09.006. Epub 2018 Sep 22.
微加工支架可有效缓解小鼠糖尿病。
Biomaterials. 2017 Aug;135:10-22. doi: 10.1016/j.biomaterials.2017.03.031. Epub 2017 Mar 27.
4
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J Biomed Mater Res A. 2017 Sep;105(9):2533-2542. doi: 10.1002/jbm.a.36101. Epub 2017 Jun 15.
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Innovative encapsulation platform based on pancreatic extracellular matrix achieve substantial insulin delivery.基于胰腺细胞外基质的创新包封平台实现了大量胰岛素的递送。
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Pancreatology. 2016 Sep-Oct;16(5):922-30. doi: 10.1016/j.pan.2016.06.007. Epub 2016 Jun 19.
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