Hyun Jiyu, Park Junhyeung, Song Jihun, Yoo Chaerim, Jang Seonmi, Lee Sang Yoon, An Jiseon, Park Hyun Su, Jung Seunghyuk, Kong Dasom, Cho Ji Hyeon, Lee Tae Il, Park Ki Dong, Im Gwang-Bum, Jeong Jee-Heon, Park Hyun-Ji, Lee Dong Yun, Bhang Suk Ho
School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Bioact Mater. 2025 May 16;51:276-292. doi: 10.1016/j.bioactmat.2025.05.005. eCollection 2025 Sep.
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 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.
为了攻克1型糖尿病（T1DM），这种疾病会因β细胞功能的胰岛素分泌减少而导致高血糖，胰岛移植已通过包括伪胰岛在内的各种策略得以发展。然而，与其他细胞结合的传统伪胰岛形成技术依赖于自然细胞聚集，这需要至少5天才能形成，甚至会出现不同细胞类型的分离，从而导致细胞活力和功能下降。在此，我们应用了一种水下独立式3D细胞培养（FS）装置，它可以通过将细胞捕获在驻波节点中来缩短球体形成时间。简而言之，在FS装置中与脂肪来源干细胞（ADSCs）一起培养以形成异型伪胰岛（Hislet），显著缩短了形成时间，不到一天。与传统伪胰岛形成方法相比，Hislet表现出细胞活力的增强。此外，ADSCs联合Hislet证明能强烈分泌各种旁分泌因子。结果还显示，与胰岛相比，Hislet对各种类型免疫细胞的血管生成作用和免疫调节作用显著增强，这可以提高移植存活率。此外，Hislet在T1DM模型中验证了葡萄糖调节能力和增强的血管生成作用。在整个这项研究中，我们提出了一种形成Hislet的新策略，该策略可以克服传统胰岛和伪胰岛在治疗T1DM方面的局限性。
