Engineering transplantable jejunal mucosal grafts using patient-derived organoids from children with intestinal failure
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Abstract
Intestinal failure, following extensive anatomical or functional loss of small intestine, has debilitating long-term consequences for children 1. The priority of patient care is to increase the length of functional intestine, particularly the jejunum, to promote nutritional independence 2. Here we construct autologous jejunal mucosal grafts using biomaterials from pediatric patients and show that patient-derived organoids can be expanded efficiently in vitro. In parallel, we generate decellularized human intestinal matrix with intact nanotopography, which forms biological scaffolds. Proteomic and Raman spectroscopy analyses reveal highly analogous biochemical profiles of human small intestine and colon scaffolds, indicating that they can be used interchangeably as platforms for intestinal engineering. Indeed, seeding of jejunal organoids onto either type of scaffold reliably reconstructs grafts that exhibit several aspects of physiological jejunal function and that survive to form luminal structures after transplantation into the kidney capsule or subcutaneous pockets of mice for up to 2 weeks. Our findings provide proof-of-concept data for engineering patient-specific jejunal grafts for children with intestinal failure, ultimately aiding in the restoration of nutritional autonomy.
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Pancreatic islets cultured in an artificial ECM were successfully engrafted into streptozocin-induced or autoimmune-driven diabetic mouse models, rescuing insulin production and reversing hyperglycemia.
“Similarly, pancreatic islets cultured in an artificial ECM could be successfully engrafted into either streptozocin-induced or autoimmune-driven diabetic mouse models, rescuing insulin production and reversing hyperglycemia147.”
From Organoids (2022) · cites this paper as [147]
The Methods section on in vivo transplantation describes jejunal grafts implanted in immunodeficient mice, not pancreatic islets in diabetic mice. Searches for artificial-ECM islet engraftment and streptozocin- or autoimmune-driven diabetes found no passage addressing insulin restoration or reversal of hyperglycemia. (LLM, conf=0.78)
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- Authors
- Meran, L., Massie, I., Campinoti, S., Weston, A. E., Gaifulina, R., Tullie, L., Faull, P., Orford, M., Kucharska, A., Baulies, A., Novellasdemunt, L., Angelis, N., Hirst, E., König, J., Tedeschi, A. M., Pellegata, A. F., Eli, S., Snijders, A. P., Collinson, L., Thapar, N., Thomas, G. M. H., Eaton, S., Bonfanti, P., De Coppi, P., & Li, V. S. W.
- Affiliations
- The Francis Crick Institute (GB)
- University College London (GB)
- Children's Health Queensland Hospital and Health Service (AU)
- Corresponding author
- Li, Vivian S. W.
- ORCID
- Meran, Laween
- Massie, Isobel
- Campinoti, Sara
- Weston, Anne E.
- Gaifulina, Riana
- Tullie, Lucinda
- Faull, Peter
- Orford, Michael
- Baulies, Anna
- Novellasdemunt, Laura
- Angelis, Nikolaos
- Hirst, Elizabeth
- Pellegata, Alessandro Filippo
- Snijders, Ambrosius P.
- Collinson, Lucy
- Thapar, Nikhil
- Thomas, Geraint M. H.
- Eaton, Simon
- Bonfanti, Paola
- De Coppi, Paolo
- Li, Vivian S. W.
- Venue
- Nature Medicine
- Published
- 2020-09-07
- Volume
- 26
- Issue
- 10
- Pages
- 1593-1601
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC7116539
- OpenAlex
- W3083160231
- Cited by
- 143
- References
- 66
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 21 · 2023: 37 · 2022: 34 · 2021: 18 · 2020: 5
- FWCI
- 21.48
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Medicine (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Virtual Community of Pathological Anatomy (University of Castilla La Mancha) (submittedVersion)
- Funders
- EC | Horizon 2020 Framework Programme (668294)
- Cancer Research UK (FC001105)
- RCUK | Medical Research Council (MRC (FC001105)
- Wellcome Trust (FC001105)
- Francis Crick Institute
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Keywords
- intestinal failure, patient-derived organoids, biological scaffolds, autologous tissue transfer, nanotopography, pediatric patients, organoid expansion, graft reconstruction, kidney capsule transplantation, Raman spectroscopy, proteomics
- MeSH terms
- Proof of Concept Study, Animals, Cell Differentiation, Cells, Cultured, Child, Extracellular Matrix, Female, Humans, Intestinal Diseases, Intestinal Mucosa, Jejunum, Mice, Transgenic, Organoids, Swine, Mice, SCID, Mice, Inbred NOD, Enterocytes, Tissue Engineering, Cell Proliferation, Mice, Tissue Scaffolds, Precision Medicine, HEK293 Cells, Primary Cell Culture, Human Umbilical Vein Endothelial Cells
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