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用于改善糖尿病研究的三维培养平台的新前沿

New Frontiers in Three-Dimensional Culture Platforms to Improve Diabetes Research.

作者信息

Mohandas Sundhar, Gayatri Vijaya, Kumaran Kriya, Gopinath Vipin, Paulmurugan Ramasamy, Ramkumar Kunka Mohanram

机构信息

Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India.

Department of Radiology, Molecular Imaging Program at Stanford, Canary Centre for Cancer Early Detection, Bio-X Program, Stanford University School of Medicine, Palo Alto, CA 94304, USA.

出版信息

Pharmaceutics. 2023 Feb 22;15(3):725. doi: 10.3390/pharmaceutics15030725.

DOI:10.3390/pharmaceutics15030725
PMID:36986591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10056755/
Abstract

Diabetes mellitus is associated with defects in islet β-cell functioning and consequent hyperglycemia resulting in multi-organ damage. Physiologically relevant models that mimic human diabetic progression are urgently needed to identify new drug targets. Three-dimensional (3D) cell-culture systems are gaining a considerable interest in diabetic disease modelling and are being utilized as platforms for diabetic drug discovery and pancreatic tissue engineering. Three-dimensional models offer a marked advantage in obtaining physiologically relevant information and improve drug selectivity over conventional 2D (two-dimensional) cultures and rodent models. Indeed, recent evidence persuasively supports the adoption of appropriate 3D cell technology in β-cell cultivation. This review article provides a considerably updated view of the benefits of employing 3D models in the experimental workflow compared to conventional animal and 2D models. We compile the latest innovations in this field and discuss the various strategies used to generate 3D culture models in diabetic research. We also critically review the advantages and the limitations of each 3D technology, with particular attention to the maintenance of β-cell morphology, functionality, and intercellular crosstalk. Furthermore, we emphasize the scope of improvement needed in the 3D culture systems employed in diabetes research and the promises they hold as excellent research platforms in managing diabetes.

摘要

糖尿病与胰岛β细胞功能缺陷以及随之而来的高血糖相关,进而导致多器官损伤。迫切需要能够模拟人类糖尿病进展的生理相关模型来确定新的药物靶点。三维(3D)细胞培养系统在糖尿病疾病建模方面正引起广泛关注,并被用作糖尿病药物研发和胰腺组织工程的平台。与传统的二维(2D)培养和啮齿动物模型相比,三维模型在获取生理相关信息以及提高药物选择性方面具有显著优势。事实上,最近的证据有力地支持了在β细胞培养中采用适当的3D细胞技术。这篇综述文章提供了一个与传统动物模型和二维模型相比,在实验流程中使用三维模型优势的最新观点。我们汇总了该领域的最新创新成果,并讨论了在糖尿病研究中用于生成三维培养模型的各种策略。我们还批判性地审视了每种三维技术的优缺点,特别关注β细胞形态、功能和细胞间相互作用的维持。此外,我们强调了糖尿病研究中使用的三维培养系统需要改进的方面以及它们作为管理糖尿病的优秀研究平台所具有的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/1f27e0eb7b7d/pharmaceutics-15-00725-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/db5f5d6d10ae/pharmaceutics-15-00725-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/7220c5a0dda3/pharmaceutics-15-00725-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/14783f12423e/pharmaceutics-15-00725-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/20541a781dc2/pharmaceutics-15-00725-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/7cd5f9df8646/pharmaceutics-15-00725-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/1f27e0eb7b7d/pharmaceutics-15-00725-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/db5f5d6d10ae/pharmaceutics-15-00725-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/7220c5a0dda3/pharmaceutics-15-00725-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/14783f12423e/pharmaceutics-15-00725-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/20541a781dc2/pharmaceutics-15-00725-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/7cd5f9df8646/pharmaceutics-15-00725-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69b8/10056755/1f27e0eb7b7d/pharmaceutics-15-00725-g006.jpg

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High-glucose 3D INS-1 cell model combined with a microfluidic circular concentration gradient generator for high throughput screening of drugs against type 2 diabetes.高糖3D INS-1细胞模型与微流控圆形浓度梯度发生器相结合用于2型糖尿病药物的高通量筛选
RSC Adv. 2018 Jul 16;8(45):25409-25416. doi: 10.1039/c8ra04040k.
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Development of scaffold-free vascularized pancreatic beta-islets in vitro models by the anchoring of cell lines to a bioligand-functionalized gelatine substrate.
纳尔逊(L.)艾氏草及其含量最高的黄酮类化合物对与糖尿病骨病相关的主要机制的有益作用。
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