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현지유Jiyu Hyun

성균관대학교

Bioact. Mater., Available online 16 May 2025 | https://doi.org/10.1016/j.bioactmat.2025.05.005 Subaqueous acoustic pressure system based one day heterotypic pseudo-islet spheroid formation with adipose derived stem cells for graft survival-related function enhancement

Jiyu Hyun ^a,1, Junhyeung Park ^b,1, Jihun Song^c,d, Chaerim Yoo ^e, Seonmi Jang ^e, Sang Yoon Lee ^a, Jiseon An ^a, Hyun Su Park ^a, Seunghyuk Jung ^f, Dasom Kong ^g, Ji Hyeon Cho ^b, Tae Il Lee ^h, Ki Dong Park ^g, Gwang-Bum Im^a,i, Jee-Heon Jeong ^b, Hyun-Ji Park ^g,j, Dong Yun Lee ^e,k, Suk Ho Bhang^a
^aSchool of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
^bDepartment of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon, 16419, Republic of Korea
^cBiomedical Research Center, Korea University Guro Hospital, Seoul, Republic of Korea
^dDepartment of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea
^eDepartment of Bioengineering, College of Engineering, Hanyang University, Seoul, 04763, Republic of Korea
^fDepartment of Applied Chemistry & Biological Engineering, Ajou University, Suwon, 16499, Republic of Korea
^gDepartment of Molecular Science and Technology, Ajou University, Suwon, 16499, Republic of Korea
^hDepartment of Materials Science and Engineering, Gachon University, Seong-nam, 13120, Republic of Korea
ⁱDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA
^jAdvanced College of Bio-Convergence Engineering, Ajou University, Suwon, 16499, Republic of Korea
^kElixir Pharmatech Inc., Seoul, 04763, Republic of Korea

¹These authors contributed equally to this work.
Corresponding authors: Jee-Heon Jeong, Hyun-Ji Park, Dong Yun Lee, Suk Ho Bhang

Abstract

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.

논문정보

형식Research article
게재일2025년 05월 (BRIC 등록일 2025-06-10)
연구진국내 연구진
분야 바이오·의료융합 > 다학제 융합/복합

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