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

Autor: Vivian S. W. Li, Michael Orford, Paolo De Coppi, Nikhil Thapar, Alessandro Filippo Pellegata, Susanna Eli, L Meran, Alfonso M Tedeschi, Simon Eaton, Sara Campinoti, Ambrosius P. Snijders, Riana Gaifulina, Elizabeth M. A. Hirst, Lucinda Tullie, Laura Novellasdemunt, Anna Baulies, Lucy M. Collinson, Anne Weston, Isobel Massie, Julia König, Paola Bonfanti, Nikolaos Angelis, Geraint M.H. Thomas, Anna Kucharska, Peter Faull
Rok vydání: 2019
Předmět:
0301 basic medicine
Pathology
Swine
Mice
SCID
Regenerative medicine
Transgenic
Jejunum
Mice
0302 clinical medicine
Tissue engineering
Mice
Inbred NOD
Medicine
Intestinal Mucosa
Precision Medicine
Child
Cells
Cultured
Decellularization
Cultured
Tissue Scaffolds
Cell Differentiation
General Medicine
3. Good health
Extracellular Matrix
Organoids
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
medicine.medical_specialty
Cells
Primary Cell Culture
Mice
Transgenic
SCID
Proof of Concept Study
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Organoid
Human Umbilical Vein Endothelial Cells
Animals
Humans
Nanotopography
Cell Proliferation
Tissue Engineering
business.industry
Small intestine
Transplantation
Intestinal Diseases
030104 developmental biology
Enterocytes
HEK293 Cells
Inbred NOD
business
Zdroj: Nature medicine. 26(10)
ISSN: 1546-170X
Popis: Intestinal failure, following extensive anatomical or functional loss of small intestine, has debilitating long-term consequences for children1. The priority of patient care is to increase the length of functional intestine, particularly the jejunum, to promote nutritional independence2. 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.
Databáze: OpenAIRE
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