論文標題Paper Title

3D Imaging Resolves Human Pancreatic Duct-β-Cell Clusters During Cystic Change

學術期刊刊名Journal Name

美國糖尿病學會官方期刊Diabetes

研究團隊 Research Team

主持人Principle Investigator：

湯學成教授  Shiue-Cheng Tang, Professor

國立清華大學醫學科學系/生物科技研究所

Department of Medical Science

Institute of Biotechnology

College of Life Science and Medicine (CLSM), National Tsing Hua University (NTHU).

參與者Participants:：

田郁文 醫師 Yu-Wen Tien, M.D., Ph.D.

國立臺灣大學醫學院附設醫院外科部

National Taiwan University Hospital, Department of Surgery

李志元 醫師 Chih-Yuan Lee, M.D., Ph.D.

國立臺灣大學醫學院附設醫院外科部

National Taiwan University Hospital, Department of Surgery

郭庭均 醫師 Ting-Chun Kuo, M.D., Ph.D.

國立臺灣大學醫學院附設醫院外科部

National Taiwan University Hospital, Department of Surgery

周亞賢 研究助理 Ya-Hsien Chou, M.S.

國立清華大學生物科技研究所

Institute of Biotechnology, College of Life Science and Medicine (CLSM), National Tsing Hua University (NTHU).

彭士容 研究助理 Shih-Jung Peng, M.S.

國立清華大學醫學科學系

Department of Medical Science, College of Life Science and Medicine (CLSM), National Tsing Hua University (NTHU).

蕭輔廷 博士 Fu-Ting Hsiao, Ph.D.

國立清華大學生物科技研究所

Institute of Biotechnology, College of Life Science and Medicine (CLSM), National Tsing Hua University (NTHU).

鍾玫馨 醫檢師 Mei-Hsin Chung, M.S.

國立臺灣大學醫院新竹臺大分院病理部

Department of Pathology, National Taiwan University Hospital Hsinchu Branch

羅麗文 博士 Li-Wen Lo, Ph.D.

中央研究院生醫轉譯研究中心

Biomedical Translation Research Center, Academia Sinica

沈家寧 研究員 Chia-Ning Shen, Ph.D., Research Fellow

中央研究院生醫轉譯研究中心

Biomedical Translation Research Center, Academia Sinica

中央研究院基因體研究中心

Genomics Research Center, Academia Sinica

簡宏任 博士 Hung-Jen Chien, Ph.D.

中央研究院基因體研究中心

Genomics Research Center, Academia Sinica

張修碧 研究助理 Hsiu-Pi Chang, Research Assistant

國立臺灣大學醫學院附設醫院外科部

National Taiwan University Hospital, Department of Surgery

陳建嘉 醫師 Chien-Chia Chen, M.D., Ph.D.

國立臺灣大學醫學院附設醫院外科部

National Taiwan University Hospital, Department of Surgery

鄭永銘 醫師 Yung-Ming Jeng, M.D., Ph.D.

國立臺灣大學醫學院附設醫院病理部

National Taiwan University Hospital, Department of Pathology

摘要

Abstract

隨著胰臟囊性病變檢出率持續增加，其對局部胰島β細胞的影響仍未被充分了解。本研究利用先進三維組織學與Airyscan超解析影像技術，針對人體胰臟組織進行分析，發現微小囊腫周圍存在特殊的胰管－β細胞群聚結構（duct-β-cell clusters），包括嵌入胰管上皮內的β細胞以及與胰管緊密相關的β細胞群集，揭示人體胰臟組織重塑過程中過去未被認識的細胞組織特徵。

透過高解析三維影像與嚴謹的組織分析，本研究進一步解析β細胞與胰管細胞的空間排列及細胞極性特徵，建立可應用於人體胰臟研究的可靠三維影像分析平台。研究成果不僅增進對人體胰臟適應性重塑機制的理解，也為探討內源性β細胞再生及糖尿病新治療策略提供重要基礎。

Pancreatic cystic changes are increasingly detected through modern medical imaging, yet their effects on local β-cell populations remain poorly understood. In this study, we applied advanced 3D histology and Airyscan super-resolution imaging to human pancreatic tissues and discovered distinct duct–β-cell clusters associated with pancreatic microcysts. These structures included β-cells embedded within ductal epithelium and organized in close association with pancreatic ducts, revealing previously unrecognized features of pancreatic tissue remodeling.

By combining high-resolution 3D imaging with artifact-controlled tissue analysis, we characterized the spatial organization of β-cells and duct cells at subcellular resolution. Our findings provide new insights into how the human pancreas adapts to benign cystic changes and establish a robust platform for studying duct–β-cell interactions in clinically relevant human tissues.

This work advances our understanding of pancreatic biology and may provide a foundation for future studies investigating endogenous β-cell regeneration and novel therapeutic strategies for diabetes.

研究成果Result/Contributions

本研究運用先進三維組織學與Airyscan超解析影像技術，首次發現與人體胰臟微小囊腫相關之胰管－β細胞群聚結構（duct-β-cell clusters）。

研究證實β細胞可存在於重塑中的胰管上皮微環境內，並呈現特定細胞極性與空間組織特徵，揭示胰臟外分泌與內分泌組織協同重塑的新現象。

• 本研究建立可有效排除囊腔自體螢光干擾之三維超解析影像分析平台，提供解析人體胰臟細胞交互作用與組織結構的重要工具。

研究結果顯示胰管－β細胞群聚可能形成特殊微環境，參與胰臟對囊性變化的適應性反應，並可能與內源性β細胞再生相關。

本成果發表於美國糖尿病學會（American Diabetes Association）官方期刊《Diabetes》，有助於深化對人體胰臟生物學與糖尿病相關病理機制的理解，並為再生醫學研究提供新的方向。

Pancreasingly detected in clinical practice, yet their effects on local β-cell populations remain poorly understood. This study addresses an important gap in our understanding of human pancreatic tissue remodeling.

Using advanced 3D histology and Airyscan super-resolution imaging, we identified previously unrecognized duct–β-cell clusters associated with pancreatic microcysts. These structures included β-cells embedded within ductal epithelium and closely associated with remodeled ductal environments.

Our findings demonstrate coordinated exocrine and endocrine remodeling during microcyst formation and reveal distinct spatial organization between β-cells and duct cells within human pancreatic lobules.

The study establishes a robust imaging platform capable of visualizing duct–β-cell interactions in human pancreas while minimizing imaging artifacts, enabling cellular and subcellular analyses in clinically relevant tissues.

These findings provide new insights into human pancreatic adaptation and suggest that duct–β-cell clusters may represent a unique microenvironment relevant to endogenous β-cell regeneration, diabetes research, and regenerative medicine.

論文連結 Paper Link

• https://www.3d-histology.com
Introduction to 3D histology platform and related imaging technologies.

• https://www.youtube.com/@tonytang6108/videos
Videos showcasing the research team's 3D imaging technologies and research achievements.

• https://x.com/3dHistology
Updates on research findings, academic activities, and recent scientific developments.

• https://reurl.cc/OrAQyR
3D super-resolution imaging enabled by anti-fade solid-state tissue embedding using a high-refractive-index polymer.

《Diabetes》同期專文評論

Bend it like Occam: ductal origin of new islet cells in human pancreas after injury.

Diabetes 74(5): 682–684, 2025.

https://diabetesjournals.org/diabetes/article/74/5/682/158072/Bend-It-Like-Occam-Ductal-Origin-of-New-Islet

本研究論文於《Diabetes》發表時，同期由期刊邀請該領域專家撰寫專文評論（Editorial Commentary），針對研究成果所揭示之胰管－β細胞關聯、胰管細胞可塑性及人體胰臟組織重塑等議題進行深入討論。此評論反映本研究對胰臟生物學與糖尿病研究領域的重要學術價值，以及其對未來人體胰島再生研究方向的潛在影響。

Accompanying Editorial Commentary in Diabetes

Bend it like Occam: ductal origin of new islet cells in human pancreas after injury.

Diabetes 74(5): 682–684, 2025.

https://diabetesjournals.org/diabetes/article/74/5/682/158072/Bend-It-Like-Occam-Ductal-Origin-of-New-Islet

The publication of this study in Diabetes was accompanied by an editorial commentary commissioned by the journal and authored by experts in the field. The commentary discusses the implications of our findings for duct–β-cell associations, ductal cell plasticity, and pancreatic tissue remodeling, highlighting the broader significance of this work for pancreatic biology and diabetes research. The accompanying commentary further underscores the potential impact of these findings on future investigations into human islet regeneration and pancreatic repair mechanisms.