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胰岛类器官的生物工程和血管化策略:迈向糖尿病治疗的进展。

Bioengineering and vascularization strategies for islet organoids: advancing toward diabetes therapy.

机构信息

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China; Shanghai Institute for Plastic and Reconstructive Surgery, China.

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China; Shanghai Institute for Plastic and Reconstructive Surgery, China; Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, China.

出版信息

Metabolism. 2024 Mar;152:155786. doi: 10.1016/j.metabol.2024.155786. Epub 2024 Jan 10.

DOI:10.1016/j.metabol.2024.155786
PMID:38211697
Abstract

Diabetes presents a pressing healthcare crisis, necessitating innovative solutions. Organoid technologies have rapidly advanced, leading to the emergence of bioengineering islet organoids as an unlimited source of insulin-producing cells for treating insulin-dependent diabetes. This advancement surpasses the need for cadaveric islet transplantation. However, clinical translation of this approach faces two major limitations: immature endocrine function and the absence of a perfusable vasculature compared to primary human islets. In this review, we summarize the latest developments in bioengineering functional islet organoids in vitro and promoting vascularization of organoid grafts before and after transplantation. We highlight the crucial roles of the vasculature in ensuring long-term survival, maturation, and functionality of islet organoids. Additionally, we discuss key considerations that must be addressed before clinical translation of islet organoid-based therapy, including functional immaturity, undesired heterogeneity, and potential tumorigenic risks.

摘要

糖尿病带来了紧迫的医疗保健危机,需要创新的解决方案。类器官技术迅速发展,导致生物工程胰岛类器官作为治疗胰岛素依赖型糖尿病的胰岛素产生细胞的无限来源的出现。这一进展超越了对尸体胰岛移植的需求。然而,这种方法的临床转化面临两个主要限制:与原代人胰岛相比,内分泌功能不成熟,以及缺乏可灌注的脉管系统。在这篇综述中,我们总结了体外生物工程功能性胰岛类器官的最新进展,以及移植前后促进类器官移植物血管生成的最新进展。我们强调了脉管系统在确保胰岛类器官的长期存活、成熟和功能方面的关键作用。此外,我们讨论了在基于胰岛类器官的治疗进行临床转化之前必须解决的关键问题,包括功能不成熟、不理想的异质性和潜在的致瘤风险。

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Bioengineering and vascularization strategies for islet organoids: advancing toward diabetes therapy.胰岛类器官的生物工程和血管化策略:迈向糖尿病治疗的进展。
Metabolism. 2024 Mar;152:155786. doi: 10.1016/j.metabol.2024.155786. Epub 2024 Jan 10.
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引用本文的文献

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World J Transplant. 2025 Sep 18;15(3):102383. doi: 10.5500/wjt.v15.i3.102383.
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Stem cell therapy for diabetes: Advances, prospects, and challenges.糖尿病的干细胞治疗:进展、前景与挑战。
World J Diabetes. 2025 Jul 15;16(7):107344. doi: 10.4239/wjd.v16.i7.107344.
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Progress in spinal cord organoid research: advancing understanding of neural development, disease modelling, and regenerative medicine.脊髓类器官研究进展:加深对神经发育、疾病建模和再生医学的理解
Biomater Transl. 2024 Nov 15;5(4):355-371. doi: 10.12336/biomatertransl.2024.04.003. eCollection 2024.
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SUN1 inhibits osteogenesis and promotes adipogenesis of human adipose-derived stem cells by regulating α-tubulin and CD36 expression.SUN1 通过调控α-微管蛋白和 CD36 的表达抑制人脂肪来源干细胞的成骨分化并促进其成脂分化。
J Cell Mol Med. 2024 Oct;28(19):e70143. doi: 10.1111/jcmm.70143.
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Ameliorating and refining islet organoids to illuminate treatment and pathogenesis of diabetes mellitus.改善和优化胰岛类器官以阐明糖尿病的治疗和发病机制。
Stem Cell Res Ther. 2024 Jun 27;15(1):188. doi: 10.1186/s13287-024-03780-7.
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The efficiency of stem cell differentiation into functional beta cells for treating insulin-requiring diabetes: Recent advances and current challenges.干细胞分化为功能性β细胞治疗胰岛素依赖型糖尿病的效率:最新进展和当前挑战。
Endocrine. 2024 Oct;86(1):1-14. doi: 10.1007/s12020-024-03855-8. Epub 2024 May 10.