基于水下声压系统的一日异型伪胰岛球体形成与脂肪干细胞移植增强存活相关功能

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2025-05-16 DOI:10.1016/j.bioactmat.2025.05.005

Jiyu Hyun , Junhyeung Park , Jihun Song , Chaerim Yoo , Seonmi Jang , Sang Yoon Lee , Jiseon An , Hyun Su Park , Seunghyuk Jung , Dasom Kong , Ji Hyeon Cho , Tae Il Lee , Ki Dong Park , Gwang-Bum Im , Jee-Heon Jeong , Hyun-Ji Park , Dong Yun Lee , Suk Ho Bhang

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引用次数: 0

摘要

1型糖尿病（T1DM）由于β细胞功能胰岛素分泌减少而导致高血糖，为了克服这种疾病，胰岛移植已经发展出包括假胰岛在内的各种策略。然而，传统的伪胰岛形成技术与其他细胞结合依赖于自然的细胞聚集，这需要至少5天的时间才能形成，甚至表现出不同细胞类型的分离，导致细胞活力和功能下降。本文采用了一种水下独立三维细胞培养装置（FS），该装置可以通过将细胞困在声波驻波节点中来缩短球体形成时间。简单地说，用脂肪源性干细胞（ADSCs）在FS装置中培养形成异型伪胰岛（Hislet），可以显著缩短形成时间，不到一天。与传统的伪胰岛形成方法相比，小胰岛的细胞活力得到了增强。此外，与Hislet结合的ADSCs能强烈分泌多种旁分泌因子。结果还表明，与胰岛相比，小毛细胞的血管生成作用和各种免疫细胞的免疫调节作用显著增强，可提高移植存活率。此外，Hislet在体内T1DM模型中验证了葡萄糖调节能力和增强血管生成作用。在本研究中，我们提出了一种新的形成Hislet的策略，该策略可以克服T1DM常规胰岛和伪胰岛的局限性。

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Subaqueous acoustic pressure system based one day heterotypic pseudo-islet spheroid formation with adipose derived stem cells for graft survival-related function enhancement

To overcome Type 1 diabetes mellitus (T1DM), which can cause hyperglycemia due to diminished insulin secretion of β-cell function, islet transplantation has been developed with various strategies including pseudo-islet. However, conventional pseudo-islet formation techniques combining with other cells depend on natural cellular aggregation, which requires at least 5 days to form and even show segregation of distinct cell types, leading to diminished cell viability and function. Herein, we applied a subaqueous free-standing 3D cell culture (FS) device, which can reduce the spheroid formation time by trapped cell in nodes of acoustic standing wave. Briefly, Culturing with adipose-derived stem cells (ADSCs) to form heterotypic pseudo-islet (Hislet) in FS device dramatically reduced formation time less than one day. Hislet demonstrated enhancement of cell viability than conventional pseudo-islet formation method. Additionally, ADSCs combined Hislet proved strong secretion of various paracrine factors. Also results showed significantly increased angiogenesis effect and immunomodulation effect for various type of immune cells in Hislet compared to islet, which can enhance transplantation survival. Furthermore, Hislet validated glucose-regulating capacity and enhanced angiogenesis effect in vivo T1DM model. Throughout this study, we propose a novel strategy for forming Hislet that can overcome the limitations of conventional Islet and pseudo-islet for T1DM.

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.