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Cited by 210

The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling

Open access
Hohwieler, Meike, Illing, Anett, Hermann, Patrick C, Mayer, Tobias, Stockmann, Marianne, Perkhofer, Lukas, Eiseler, Tim, Antony, Justin S, Müller, Martin, Renz, Susanne, Kuo, Chao-Chung, Lin, Qiong, Sendler, Matthias, Breunig, Markus, Kleiderman, Susanne M, Lechel, André, Zenker, Martin, Leichsenring, Michael, Rosendahl, Jonas, Zenke, Martin, Sainz, Bruno, Mayerle, Julia, Costa, Ivan G, Seufferlein, Thomas, Kormann, Michael, Wagner, Martin, Liebau, Stefan, Kleger, Alexander·2017·Gut

Abstract

Objective: The generation of acinar and ductal cells from human pluripotent stem cells (PSCs) is a poorly studied process, although various diseases arise from this compartment. Design: We designed a straightforward approach to direct human PSCs towards pancreatic organoids resembling acinar and ductal progeny. Results: Extensive phenotyping of the organoids not only shows the appropriate marker profile but also ultrastructural, global gene expression and functional hallmarks of the human pancreas in the dish. Upon orthotopic transplantation into immunodeficient mice, these organoids form normal pancreatic ducts and acinar tissue resembling fetal human pancreas without evidence of tumour formation or transformation. Finally, we implemented this unique phenotyping tool as a model to study the pancreatic facets of cystic fibrosis (CF). For the first time, we provide evidence that in vitro, but also in our xenograft transplantation assay, pancreatic commitment occurs generally unhindered in CF. Importantly, cystic fibrosis transmembrane conductance regulator (CFTR) activation in mutated pancreatic organoids not only mirrors the CF phenotype in functional assays but also at a global expression level. We also conducted a scalable proof-of-concept screen in CF pancreatic organoids using a set of CFTR correctors and activators, and established an mRNA-mediated gene therapy approach in CF organoids. Conclusions: Taken together, our platform provides novel opportunities to model pancreatic disease and development, screen for disease-rescuing agents and to test therapeutic procedures.

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Metadata

Authors
Hohwieler, M., Illing, A., Hermann, P. C., Mayer, T., Stockmann, M., Perkhofer, L., Eiseler, T., Antony, J. S., Müller, M., Renz, S., Kuo, C.-C., Lin, Q., Sendler, M., Breunig, M., Kleiderman, S. M., Lechel, A., Zenker, M., Leichsenring, M., Rosendahl, J., Zenke, M., Sainz, B., Mayerle, J., Costa, I. G., Seufferlein, T., Kormann, M., Wagner, M., Liebau, S., & Kleger, A.
Venue
Gut
Publisher
BMJ
Published
2016-09-15
Volume
66
Issue
3
Pages
473-486
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
OpenAlex
W2520537726
Cited by
210
References
10
FWCI
18.92
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling. https://app.cochat.ai/papers/10.1136/gutjnl-2016-312423
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Hohwieler, M., Illing, A., Hermann, P. C., Mayer, T., Stockmann, M., Perkhofer, L., Eiseler, T., Antony, J. S., Müller, M., Renz, S., Kuo, C.-C., Lin, Q., Sendler, M., Breunig, M., Kleiderman, S. M., Lechel, A., Zenker, M., Leichsenring, M., Rosendahl, J., . . . Kleger, A. (2017). Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling. Gut. https://doi.org/10.1136/gutjnl-2016-312423

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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