In a first step toward developing autologous tissue grafts for the treatment of children with intestinal failure, patient-derived jejunal organoids seeded on scaffolds of decellularized human intestinal matrix formed grafts that had jejunal properties and formed luminal structures when transplanted into mice.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.

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

Pellegata, Alessandro Filippo;Eli, Susanna;
2020-01-01

Abstract

In a first step toward developing autologous tissue grafts for the treatment of children with intestinal failure, patient-derived jejunal organoids seeded on scaffolds of decellularized human intestinal matrix formed grafts that had jejunal properties and formed luminal structures when transplanted into mice.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.
2020
Animals
Cell Differentiation
Cell Proliferation
Cells, Cultured
Child
Enterocytes
Extracellular Matrix
Female
HEK293 Cells
Human Umbilical Vein Endothelial Cells
Humans
Intestinal Diseases
Intestinal Mucosa
Jejunum
Mice
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Organoids
Precision Medicine
Primary Cell Culture
Proof of Concept Study
Swine
Tissue Engineering
Tissue Scaffolds
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11311/1221571
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