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

ABSTRACT: Intestinal failure (IF), following extensive anatomical or functional loss of small intestine (SI), hasdebilitating long-term consequences on children1. Priority of care is to increase the child’s length of functional intestine, jejunum in particular, to promote nutritional independence2. Here we construct autologous jejunal mucosal grafts using primary patient biomaterials. We show that organoids derived from patients can be expanded efficiently in vitro. In parallel, we generate decellularized human intestinal matrix with intact nanotopography, which form optimal biological scaffolds. Remarkably, proteomic and Raman spectroscopy analyses reveal highly analogous biochemical profiles of human SI and colon scaffolds, indicating that both can be used interchangeably as platforms for intestinal engineering. Indeed, seeding jejunal organoids onto either scaffold type reliably reconstructs grafts that exhibit several aspects of physiological jejunal function with potential to survive after transplantation. Our findings provide proof-of-concept data for engineering IF patient-specific jejunal grafts, ultimately aiding in restoration of nutritional autonomy.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon, Small Intestine

SUBMITTER: Peter Faull

LAB HEAD: Bram Snijders

PROVIDER: PXD019816 | Pride | 2020-09-16

REPOSITORIES: Pride

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

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