Enhanced viability and functional maturity of iPSC-derived islet organoids by collagen-VI-enriched ECM scaffolds

IF 19.8 1区医学 Q1 CELL & TISSUE ENGINEERING

Cell stem cell Pub Date : 2025-02-24 DOI:10.1016/j.stem.2025.02.001

Deliang Zhu, Zixin Chen, Kaimin Guo, Qingqiang Xie, Yuxiu Zou, Qizheng Mou, Zhongjun Zhou, Guoxiang Jin

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引用次数: 0

Abstract

Islet organoids derived from pluripotent stem cells offer a promising solution for the shortage of cadaveric donors in diabetes treatment. However, challenges remain in improving their differentiation, viability, functional maturity, and engraftment. Here, we generated improved islet organoids with high viability and functionality by employing extracellular matrix (ECM) hydrogel of decellularized amniotic membrane (dAM). The dAM sheet facilitates islet organoid engraftment and rapidly restores normoglycemia in diabetic mice, accompanied by increased body weight and augmented insulin release in response to glucose. Interestingly, collagen VI (Col VI) was identified as a key component of islet niche, enhancing islet cell viability and biological function. Col-VI-based biomimetic ECM recapitulates the native environment and exhibits superior physiological properties. Importantly, the cellular composition and endocrine function of optimized induced pluripotent stem cell (iPSC)-derived islet organoids are comparable with those of human islets. Our findings offer a valuable platform for future endeavors in organoid-transplantation-based therapy of diabetes.

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利用富含胶原vi的ECM支架增强ipsc衍生的胰岛类器官的活力和功能成熟度

多能干细胞衍生的胰岛类器官为糖尿病治疗中尸体供体短缺提供了一个有希望的解决方案。然而，在提高它们的分化、生存能力、功能成熟度和移植方面仍然存在挑战。在这里，我们利用脱细胞羊膜（dAM）的细胞外基质（ECM）水凝胶生成了具有高活力和功能的改进的胰岛类器官。dAM薄片促进胰岛类器官的植入，并迅速恢复糖尿病小鼠的正常血糖，同时伴随着体重的增加和胰岛素释放的增加。有趣的是，胶原VI （Col VI）被认为是胰岛生态位的关键成分，可以提高胰岛细胞的活力和生物学功能。基于coli - vi的仿生ECM再现了自然环境，并表现出优越的生理特性。重要的是，优化后的诱导多能干细胞（iPSC）衍生的胰岛类器官的细胞组成和内分泌功能与人类胰岛相当。我们的发现为未来以类器官移植为基础的糖尿病治疗提供了一个有价值的平台。

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来源期刊

Cell stem cell 生物-细胞生物学

CiteScore

37.10

自引率

2.50%

发文量

151

审稿时长

42 days

期刊介绍： Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.