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INtestinal Tissue ENgineering Solution

Deliverables

Dissemination event with patient groups

The consortium will organize a patient and families dissemination event which will be communicating results as well as receiving input from patients and their families. The event will be organised in collaboration with the three patient support groups associated to the project

Tool for engaging the public

A new tool for engaging publics, including school students and patients, around short bowel syndrome, and potential clinical uses of intestinal stem cells.

Analysis of TEI in mouse

We will deliver a histological, immunohistochemical and morphometric description of implanted TEI in the mouse.

Guidelines for quality assessment of intestinal cell lineages utilised for transplantation

The consortium members will draft an open letter to be published, which describes the minimum requirement for quality assessment of intestinal cell lineages if they are to be implemented for therapeutic transplantation.

Obtaining tissue

We will set up a standard Operating Procedure for obtaining the tissue sample that is required for the in vitro procedure up to the transplantation. The protocol will describe the regulatory approval, the logistics and the technical description of the isolation up to taking it into culture.

Report on dissemination of project outcomes, patient engagement and mobility program

A report summarizing the dissemination of project outcome, patient engagement and mobility program. Will include lessons learned and suggested improvements for future projects.

Website

Creation and launch of INTENS project-specific website at www.intens.info as well as linking from EuroStemCell, PINNT, Short Gut Foundation and other relevant websites.

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Publications

Homeostatic mini-intestines through scaffold-guided organoid morphogenesis

Author(s): Mikhail Nikolaev, Olga Mitrofanova, Nicolas Broguiere, Sara Geraldo, Devanjali Dutta, Yoji Tabata, Bilge Elci, Nathalie Brandenberg, Irina Kolotuev, Nikolce Gjorevski, Hans Clevers, Matthias P. Lutolf
Published in: Nature, Issue 585/7826, 2020, Page(s) 574-578, ISSN 0028-0836
DOI: 10.1038/s41586-020-2724-8

NEDD4 and NEDD4L regulate Wnt signalling and intestinal stem cell priming by degrading LGR5 receptor

Author(s): Laura Novellasdemunt, Anna Kucharska, Cara Jamieson, Maria Prange‐Barczynska, Anna Baulies, Pedro Antas, Jelte van der Vaart, Helmuth Gehart, Madelon M Maurice, Vivian SW Li
Published in: The EMBO Journal, Issue 39/3, 2019, ISSN 0261-4189
DOI: 10.15252/embj.2019102771

Tissue-Engineering the Intestine: The Trials before the Trials

Author(s): Hans Clevers, Ryan K. Conder, Vivian S.W. Li, Matthias P. Lutolf, Ludovic Vallier, Sarah Chan, Tracy C. Grikscheit, Kim B. Jensen, Paolo De Coppi
Published in: Cell Stem Cell, Issue 24/6, 2019, Page(s) 855-859, ISSN 1934-5909
DOI: 10.1016/j.stem.2019.04.018

Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture

Author(s): Giovanni Giuseppe Giobbe, Claire Crowley, Camilla Luni, Sara Campinoti, Moustafa Khedr, Kai Kretzschmar, Martina Maria De Santis, Elisa Zambaiti, Federica Michielin, Laween Meran, Qianjiang Hu, Gijs van Son, Luca Urbani, Anna Manfredi, Monica Giomo, Simon Eaton, Davide Cacchiarelli, Vivian S. W. Li, Hans Clevers, Paola Bonfanti, Nicola Elvassore, Paolo De Coppi
Published in: Nature Communications, Issue 10/1, 2019, ISSN 2041-1723
DOI: 10.1038/s41467-019-13605-4

Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation

Author(s): Giovanni Canu, Emmanouil Athanasiadis, Rodrigo A. Grandy, Jose Garcia-Bernardo, Paulina M. Strzelecka, Ludovic Vallier, Daniel Ortmann, Ana Cvejic
Published in: Genome Biology, Issue 21/1, 2020, ISSN 1474-760X
DOI: 10.1186/s13059-020-02058-4

Genome-Wide Epigenetic and Transcriptomic Characterization of Human-Induced Pluripotent Stem Cell–Derived Intestinal Epithelial Organoids

Author(s): Judith Kraiczy, Alexander D.B. Ross, Jessica L. Forbester, Gordon Dougan, Ludovic Vallier, Matthias Zilbauer
Published in: Cellular and Molecular Gastroenterology and Hepatology, Issue 7/2, 2019, Page(s) 285-288, ISSN 2352-345X
DOI: 10.1016/j.jcmgh.2018.10.008

The Transcription Co-Repressors MTG8 and MTG16 Regulate Exit of Intestinal Stem Cells From Their Niche and Differentiation Into Enterocyte vs Secretory Lineages

Author(s): Anna Baulies, Nikolaos Angelis, Valentina Foglizzo, E. Thomas Danielsen, Harshil Patel, Laura Novellasdemunt, Anna Kucharska, Joana Carvalho, Emma Nye, Paolo De Coppi, Vivian S.W. Li
Published in: Gastroenterology, 2020, ISSN 0016-5085
DOI: 10.1053/j.gastro.2020.06.012

Tracing the origin of adult intestinal stem cells

Author(s): Jordi Guiu, Edouard Hannezo, Shiro Yui, Samuel Demharter, Svetlana Ulyanchenko, Martti Maimets, Anne Jørgensen, Signe Perlman, Lene Lundvall, Linn Salto Mamsen, Agnete Larsen, Rasmus H. Olesen, Claus Yding Andersen, Lea Langhoff Thuesen, Kristine Juul Hare, Tune H. Pers, Konstantin Khodosevich, Benjamin D. Simons, Kim B. Jensen
Published in: Nature, Issue 570/7759, 2019, Page(s) 107-111, ISSN 0028-0836
DOI: 10.1038/s41586-019-1212-5

The hope and the hype of organoid research

Author(s): Meritxell Huch, Juergen A. Knoblich, Matthias P. Lutolf, Alfonso Martinez-Arias
Published in: Development, Issue 144/6, 2017, Page(s) 938-941, ISSN 0950-1991
DOI: 10.1242/dev.150201

Multiscale microenvironmental perturbation of pluripotent stem cell fate and self-organization

Author(s): Yoji Tabata, Matthias P. Lutolf
Published in: Scientific Reports, Issue 7/1, 2017, ISSN 2045-2322
DOI: 10.1038/srep44711

Progress and potential in organoid research

Author(s): Giuliana Rossi, Andrea Manfrin, Matthias P. Lutolf
Published in: Nature Reviews Genetics, Issue 19/11, 2018, Page(s) 671-687, ISSN 1471-0056
DOI: 10.1038/s41576-018-0051-9

YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration

Author(s): Shiro Yui, Luca Azzolin, Martti Maimets, Marianne Terndrup Pedersen, Robert P. Fordham, Stine L. Hansen, Hjalte L. Larsen, Jordi Guiu, Mariana R.P. Alves, Carsten F. Rundsten, Jens V. Johansen, Yuan Li, Chris D. Madsen, Tetsuya Nakamura, Mamoru Watanabe, Ole H. Nielsen, Pawel J. Schweiger, Stefano Piccolo, Kim B. Jensen
Published in: Cell Stem Cell, Issue 22/1, 2018, Page(s) 35-49.e7, ISSN 1934-5909
DOI: 10.1016/j.stem.2017.11.001

Mammalian body plan engineering: Lessons and challenges

Author(s): Alfonso Martinez Arias, Matthias P. Lutolf
Published in: Current Opinion in Systems Biology, Issue 11, 2018, Page(s) 50-56, ISSN 2452-3100
DOI: 10.1016/j.coisb.2018.07.007

Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon

Author(s): Conor J. McCann, Julie E. Cooper, Dipa Natarajan, Benjamin Jevans, Laura E. Burnett, Alan J. Burns, Nikhil Thapar
Published in: Nature Communications, Issue 8, 2017, Page(s) 15937, ISSN 2041-1723
DOI: 10.1038/ncomms15937

Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling

Author(s): Claudia Y. Janda, Luke T. Dang, Changjiang You, Junlei Chang, Wim de Lau, Zhendong A. Zhong, Kelley S. Yan, Owen Marecic, Dirk Siepe, Xingnan Li, James D. Moody, Bart O. Williams, Hans Clevers, Jacob Piehler, David Baker, Calvin J. Kuo, K. Christopher Garcia
Published in: Nature, Issue 545/7653, 2017, Page(s) 234-237, ISSN 0028-0836
DOI: 10.1038/nature22306

Establishing Proximal and Distal Regional Identities in Murine and Human Tissue-Engineered Lung and Trachea

Author(s): Andrew Trecartin, Soula Danopoulos, Ryan Spurrier, Hanaa Knaneh-Monem, Michael Hiatt, Barbara Driscoll, Christian Hochstim, Denise Al-Alam, Tracy C. Grikscheit
Published in: Tissue Engineering Part C: Methods, Issue 22/11, 2016, Page(s) 1049-1057, ISSN 1937-3384
DOI: 10.1089/ten.TEC.2016.0261

Functional Human and Murine Tissue-Engineered Liver Is Generated from Adult Stem/Progenitor Cells

Author(s): Nirmala Mavila, Andrew Trecartin, Ryan Spurrier, Yi Xiao, Xiaogang Hou, David James, Xiaowei Fu, Brian Truong, Clara Wang, Gerald S. Lipshutz, Kasper S. Wang, Tracy C. Grikscheit
Published in: STEM CELLS Translational Medicine, Issue 6/1, 2017, Page(s) 238-248, ISSN 2157-6564
DOI: 10.5966/sctm.2016-0205

DNA methylation defines regional identity of human intestinal epithelial organoids and undergoes dynamic changes during development

Author(s): Judith Kraiczy, Komal M Nayak, Kate J Howell, Alexander Ross, Jessica Forbester, Camilla Salvestrini, Roxana Mustata, Sally Perkins, Amanda Andersson-Rolf, Esther Leenen, Anke Liebert, Ludovic Vallier, Philip C Rosenstiel, Oliver Stegle, Gordon Dougan, Robert Heuschkel, Bon-Kyoung Koo, Matthias Zilbauer
Published in: Gut, Issue 68/1, 2018, Page(s) 49-61, ISSN 0017-5749
DOI: 10.1136/gutjnl-2017-314817

Low‐Defect Thiol‐Michael Addition Hydrogels as Matrigel Substitutes for Epithelial Organoid Derivation

Author(s): Saba Rezakhani, Nikolce Gjorevski, Matthias P. Lutolf
Published in: Advanced Functional Materials, 2020, Page(s) 2000761, ISSN 1616-301X
DOI: 10.1002/adfm.202000761

SH3BP4 Regulates Intestinal Stem Cells and Tumorigenesis by Modulating β-Catenin Nuclear Localization

Author(s): Pedro Antas, Laura Novellasdemunt, Anna Kucharska, Isobel Massie, Joana Carvalho, Dahmane Oukrif, Emma Nye, Marco Novelli, Vivian S.W. Li
Published in: Cell Reports, Issue 26/9, 2019, Page(s) 2266-2273.e4, ISSN 2211-1247
DOI: 10.1016/j.celrep.2019.01.110

A Novel Human Pluripotent Stem Cell-Derived Neural Crest Model of Treacher Collins Syndrome Shows Defects in Cell Death and Migration

Author(s): Felipe Serrano, William George Bernard, Alessandra Granata, Dharini Iyer, Ben Steventon, Matthew Kim, Ludovic Vallier, Laure Gambardella, Sanjay Sinha
Published in: Stem Cells and Development, Issue 28/2, 2019, Page(s) 81-100, ISSN 1547-3287
DOI: 10.1089/scd.2017.0234

Engineering transplantable jejunal mucosal grafts using patient-derived organoids from children with intestinal failure

Author(s): Laween Meran, Isobel Massie, Sara Campinoti, Anne E. Weston, Riana Gaifulina, Lucinda Tullie, Peter Faull, Michael Orford, Anna Kucharska, Anna Baulies, Laura Novellasdemunt, Nikolaos Angelis, Elizabeth Hirst, Julia König, Alfonso Maria Tedeschi, Alessandro Filippo Pellegata, Susanna Eli, Ambrosius P. Snijders, Lucy Collinson, Nikhil Thapar, Geraint M. H. Thomas, Simon Eaton, Paola Bonfanti, Paol
Published in: Nature Medicine, 2019, ISSN 1078-8956
DOI: 10.1038/s41591-020-1024-z