INtestinal Tissue ENgineering Solution

Project Information

INTENS

Grant agreement ID: 668294

DOI 10.3030/668294

Project closed

EC signature date 9 December 2015

Start date 1 January 2016

End date 30 September 2022

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost € 7 101 716,25

EU contribution € 5 990 464,00

Coordinated by

UNIVERSITY COLLEGE LONDON
United Kingdom

Deliverables

Other (2)

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.

Documents, reports (8)

SOP for the cell culture methods

A Standard operating procedure for obtaining expanding and seeding of cells on a scaffold for the purpose of transplantation

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.

Outcome and function of TEI in piglets

Survival and weight gain of piglets with TEI implanted in the omentum will be described TEI will be characterized morphometrically and histologically and the function of the TEI also characterized with comparison between iPS and postnatal stem cell based implants

Report on health economics related to INTENS objectives

Produce a report based on information gathering from leading social scientists whose research already addresses these areas and make their findings available in the public domain

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.

Outcome and function of small bowel mucosa in large bowel in piglets

Survival and weight gain of piglets with engineered small bowel mucosa implanted in the large bowel in substitution of colonic mucosa will be described Function will be characterized and engineered mucosa characterized morphometrically and histologically with comparison between iPS and postnatal stem cell based implants

Websites, patent fillings, videos etc. (1)

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.

Publications

Peer reviewed articles (23)

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
Publisher: Nature Publishing Group
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
Publisher: Nature Publishing Group
DOI: 10.15252/embj.2019102771

Building gut from scratch — progress and update of intestinal tissue engineering

Author(s): Tullie L, Jones BC, De Coppi P, Li VSW
Published in: Nature Reviews Gastroenterology and Hepatology, Issue 19, 2022, Page(s) 417-431, ISSN 1759-5045
Publisher: Nature Publishing Group
DOI: 10.1038/s41575-022-00586-x

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
Publisher: Cell Press
DOI: 10.1016/j.stem.2019.04.018

Bioengineering human intestinal mucosal grafts using patient derived organoids, fibroblasts and scaffolds

Author(s): Meran L, Tullie L, Eaton S, De Coppi P, Li V
Published in: Nature Protocols, Issue 18, 2023, Page(s) 108-135, ISSN 1750-2799
Publisher: Springer Nature
DOI: 10.1038/s41596-022-00751-1

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
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-019-13605-4

Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling

Author(s): "Martti Maimets1,2,3 #, Marianne Terndrup Pedersen1,2, #, Jordi Guiu1,2, Jes Dreier2,4, Malte Thodberg1,2,5, Yasuko Antoku1, Pawel J. Schweiger1,2, Leonor Rib1, Raul Bardini Bressan1,2,3, Yi Miao6, K. Christopher Garcia6,7, Albin Sandelin1,5, Palle Serup2,3 and Kim B. Jensen1,2,3*"
Published in: Nature Communications, Issue Vol 13 (article no. 715), 2022, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-022-28369-7

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
Publisher: Elsevier Inc.
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
Publisher: W. B. Saunders Co., Ltd.
DOI: 10.1053/j.gastro.2020.06.012

Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn’s Disease

Author(s): Rasa Elmentaite et al
Published in: Developmental Cell, Issue 00222593, 2020, ISSN 0022-2593
Publisher: British Medical Association
DOI: 10.1016/j.devcel.2020.11.010

A Perfusion Bioreactor for Longitudinal Monitoring of Bioengineered Liver Constructs

Author(s): Sassi, L; Ajayi, O; Campinoti, S; Natarajan, D; McQuitty, C; Siena, RR; Mantero, S; De Coppi, P; Pellegata, AF; Chokshi, S; Urbani, L
Published in: Nanomaterials, Issue 20794991, 2021, ISSN 2079-4991
Publisher: MDPI
DOI: 10.3390/nano11020275

SARS-CoV-2 infection and replication in human gastric organoids.

Author(s): Giovanni Giuseppe Giobbe; Francesco Bonfante; Brendan C. Jones; Onelia Gagliano; Camilla Luni; Elisa Zambaiti; Elisa Zambaiti; Silvia Perin; Cecilia Laterza; Georg A. Busslinger; Hannah T. Stuart; Matteo Pagliari; Alessio Bortolami; Eva Mazzetto; Anna Manfredi; Chiara Colantuono; Lucio Di Filippo; Alessandro Filippo Pellegata; Valentina Panzarin; Nikhil Thapar; Vivian S. W. Li; Simon Eaton; Davide
Published in: Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021), Issue 20411723, 2021, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-021-26762-2

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
Publisher: Nature Publishing Group
DOI: 10.1038/s41586-019-1212-5

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
Publisher: Nature Publishing Group
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
Publisher: Cell Press
DOI: 10.1016/j.stem.2017.11.001

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
Publisher: Nature Publishing Group
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
Publisher: Nature Publishing Group
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
Publisher: Mary Ann Liebert Inc.
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
Publisher: AlphaMed Press
DOI: 10.5966/sctm.2016-0205

Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation

Author(s): GW-He, L Lin, J DeMartino , X Zheng, N Staliarova, T Dayton, H Begthel, WJ van de Wetering , E Bodewes, J van Zon, S Tans, C Lopez-Iglesias, PJ Peters, W Wu, D Kotlarz, C Klein, T Margaritis, F Holstege, H Clevers
Published in: Cell Stem Cell. 2022, Issue 29(9), 2022, Page(s) 1333-1345, ISSN 1875-9777
Publisher: Elsevier
DOI: 10.1016/j.stem.2022.08.002

Paediatric gastric organoids as a tool for disease modelling and clinical translation

Author(s): Brendan C. Jones, Giuseppe Calà, Paolo De Coppi & Giovanni Giuseppe Giobbe
Published in: Pediatric Surgery International, Issue 01790358, 2021, ISSN 0179-0358
Publisher: Springer Verlag
DOI: 10.1007/s00383-020-04821-x

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
Publisher: Cell Press
DOI: 10.1016/j.celrep.2019.01.110

Adaptable haemodynamic endothelial cells for organogenesis and tumorigenesis

Author(s): Palikuqi, B; Nguyen, DHT; Li, G; Schreiner, R; Pellegata, AF; Liu, Y; Redmond, D; Geng, FQ; Lin, Y; Gomez-Salinero, JM; Yokoyama, M; Zumbo, P; Zhang, T; Kunar, B; Witherspoon, M; Han, T; Tedeschi, AM; Scottoni, F; Lipkin, SM; Dow, L; Elemento, O; Xiang, JZ; Shido, K; Spence, JR; Zhou, QJ; Schwartz, RE; De Coppi, P; Rabbany, SY; Rafii, S
Published in: Nature, Issue 14764687, 2020, ISSN 1476-4687
Publisher: Nature Research
DOI: 10.1038/s41586-020-2712-z

Non-peer reviewed articles (1)

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
Publisher: Nature Publishing Group
DOI: 10.1038/s41591-020-1024-z