A convective transport-enhanced multi-organoid device for therapeutic modeling of the liver-pancreas axis in obesity

Sep 28, 2026

Uploaded by Jiven

Obesity-associated metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) are rising, creating a need for physiologically relevant liver–pancreas in vitro models. Existing multi-organoid systems inadequately reproduce complex, directional metabolic interactions due to passive-diffusion exchange and shared or non-compartmentalized media. To address this, a multi-organoid device integrates convective flow with physically separated liver and pancreatic organoid environments.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

Introduction

Background and need for improved models

Methods

Device design and evaluation assays

Results

Enhanced directional transport and preserved organoid function

Conclusion

Modeling of MASLD–T2DM metabolic cascade

Theranostics 2026, Vol. 16, Issue 1 Ivyspring International Publisher 220 Theranostics 2026; 16(1): 220-238. doi: 10.7150/thno.114415 Research Paper A convective transport–enhanced multi–organoid device for therapeutic modeling of the liver–pancreas axis in obesity Jisu Kim1*, Jungho Bae2*, Baofang Cui2, Seung-Woo Cho2,3,4􀀍, Kisuk Yang1,5,6􀀍 1. Department of Bioengineering and Nano-Bioengineering, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea. 2. Department of Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea. 3. Center for Nanomedicine, Institute for Basic Science (IBS), Seoul, 03722, Republic of Korea. 4. Cellartgen Inc., Seoul, 03722, Republic of Korea. 5. Division of Bioengineering, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea. 6. Research Center for Bio Materials & Process Development, Incheon National University, Incheon, 22012, Republic of Korea. *J. K. and J. B. contributed equally to this work. 􀀍 Corresponding authors: Prof. Seung-Woo Cho, Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea; E-mail: [seungwoocho@yonsei.ac.kr. Prof. Kisuk](seungwoocho@yonsei.ac.kr. Prof. Kisuk) Yang, Division of Bioengineering, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea; [E-mail: kisuky@inu.ac.kr](E-mail: kisuky@inu.ac.kr). © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions. Received: 2025.03.25; Accepted: 2025.09.08; Published: 2026.01.01 Abstract Rationale: Obesity-associated metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) are increasing rapidly, necessitating physiologically relevant in vitro models of the liver–pancreas axis. While recent multi-organoid systems have advanced inter-organ modeling, many systems still fall short of replicating the complex and directional metabolic interactions required to accurately reflect disease progression. This is partly due to inherent limitations such as reliance on passive diffusion for metabolic exchange and the use of shared or non-compartmentalized media, which restrict tissue-specific functions and fail to mimic in vivo-like physiological gradients. Methods: To overcome these limitations, we developed a multi-organoid device (MOD) that incorporates convective flow and physically separates liver and pancreatic organoids in distinct media environments. To evaluate the effectiveness of this co-culture system, we assessed metabolic transport using FITC-dextran and examined pancreatic and liver organoid function by measuring insulin and albumin secretion respectively. The effectiveness of the MOD in modeling MASLD-induced T2DM was further validated through functional assays and transcriptomic analysis. Results: The MOD successfully recapitulated key pathological features of MASLD-induced T2DM. Convective flow significantly enhanced directional transport of glucose and other metabolic molecules compared to passive diffusion, as validated by simulation and diffusion assays. Media separation preserved organoid function, increasing insulin and albumin secretion by 1.8-and 1.6-fold, respectively, compared with the non-separated group. Importantly, the device achieved rapid glucose regulation following glucose stimulation, with normoglycemia restored within 2 hours closely mimicking physiological glucose regulation not previously attainable in existing systems. Under MASLD conditions, the platform further revealed that liver-derived Fetuin-A was associated with β-cell a

FAQs

What problem does the study address in multi-organoid liver–pancreas modeling?

It targets the inability of many systems to reproduce complex, directional metabolic interactions, largely because they rely on passive diffusion and use shared or non-compartmentalized media.

How does the proposed multi-organoid device improve metabolic transport?

It incorporates convective flow and physically separates liver and pancreatic organoids into distinct media environments, enhancing directional transport compared with passive diffusion.

What key outcomes demonstrate its usefulness for modeling MASLD-induced T2DM?

The device recapitulates pathological features, restores normoglycemia within about 2 hours after glucose stimulation, and links liver-derived Fetuin-A to β-cell apoptosis under MASLD conditions.

Sep 28, 2026

Uploaded by Jiven