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胰腺类器官在治疗研究中的应用与挑战

Application and challenge of pancreatic organoids in therapeutic research.

作者信息

Chen Jin, Lu Jin, Wang Shu-Na, Miao Chao-Yu

机构信息

Department of Endocrinology and Metabolism, Changhai Hospital, Second Military University /Naval Medical University, Shanghai, China.

Department of Pharmacology, Second Military Medical University /Naval Medical University, Shanghai, China.

出版信息

Front Pharmacol. 2024 May 24;15:1366417. doi: 10.3389/fphar.2024.1366417. eCollection 2024.

DOI:10.3389/fphar.2024.1366417
PMID:38855754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11157021/
Abstract

The non-human primate animal and cell disease models play a crucial part in the study of the mechanisms underlying the occurrence and development of pancreatic diseases, but with increasingly prominent limitations with in-depth research. Organoids derived from human pluripotent and adult stem cells resemble human organs in their cellular composition, spatial tissue structure and physiological function, making them as an advantageous research tool. Up until now, numerous human organoids, including pancreas, have been effectively developed, demonstrating significant potential for research in organ development, disease modeling, drug screening, and regenerative medicine. However, different from intestine, liver and other organs, the pancreas is the only special organ in the human body, consisting of an exocrine gland and an endocrine gland. Thus, the development of pancreatic organoid technology faces greater challenges, and how to construct a composite pancreatic organoid with exocrine and endocrine gland is still difficult in current research. By reviewing the fundamental architecture and physiological role of the human pancreas, along with the swiftly developing domain of pancreatic organoids, we summarize the method and characteristics of human pancreatic organoids, and its application in modeling pancreatic diseases, as a platform for individualized drug screening and in regenerative medicine study. As the first comprehensive review that focus on the pharmacological study of human pancreatic organoid, the review hopes to help scholars to have a deeper understanding in the study of pancreatic organoid.

摘要

非人灵长类动物和细胞疾病模型在胰腺疾病发生发展机制的研究中发挥着关键作用,但随着研究的深入,其局限性日益突出。源自人类多能干细胞和成体干细胞的类器官在细胞组成、空间组织结构和生理功能上与人类器官相似,使其成为一种优势研究工具。截至目前,包括胰腺在内的多种人类类器官已被有效构建,在器官发育、疾病建模、药物筛选和再生医学研究中展现出巨大潜力。然而,与肠道、肝脏等器官不同,胰腺是人体唯一由外分泌腺和内分泌腺组成的特殊器官。因此,胰腺类器官技术的发展面临更大挑战,如何构建具有外分泌腺和内分泌腺的复合胰腺类器官仍是当前研究中的难题。通过回顾人类胰腺的基本结构和生理作用,以及胰腺类器官快速发展的领域,我们总结了人类胰腺类器官的构建方法和特点,及其在胰腺疾病建模、个体化药物筛选平台和再生医学研究中的应用。作为第一篇聚焦人类胰腺类器官药理学研究的综述,希望能帮助学者们在胰腺类器官研究方面有更深入的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0a/11157021/76c42e7f2815/fphar-15-1366417-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0a/11157021/340d4e699d3d/fphar-15-1366417-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0a/11157021/76c42e7f2815/fphar-15-1366417-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0a/11157021/340d4e699d3d/fphar-15-1366417-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0a/11157021/76c42e7f2815/fphar-15-1366417-g002.jpg

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Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer.
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