RT Journal Article
SR Electronic
T1 Engineering transplantable jejunal mucosal grafts using primary patient-derived organoids from children with intestinal failure
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 854083
DO 10.1101/854083
A1 Laween Meran
A1 Isobel Massie
A1 Anne Weston
A1 Riana Gaifulina
A1 Peter Faull
A1 Michael Orford
A1 Anna Kucharska
A1 Anna Baulies
A1 Elizabeth Hirst
A1 Julia Konig
A1 Alfonso Maria Tedeschi
A1 Alessandro Filippo Pellegata
A1 Susanna Eli
A1 Ambrosius P. Snijders
A1 Lucy Collinson
A1 Nikhil Thapar
A1 Geriant Thomas
A1 Simon Eaton
A1 Paola Bonfanti
A1 Paolo De Coppi
A1 Vivian S.W. Li
YR 2019
UL http://biorxiv.org/content/early/2019/11/25/854083.abstract
AB Intestinal failure (IF), following extensive anatomical or functional loss of small intestine (SI), has debilitating long-term effects on infants and children with this condition. Priority of care is to increase the child’s length of functional intestine, jejunum in particular, to improve nutritional independence. Here we report a robust protocol for reconstruction of autologous intestinal mucosal grafts using primary IF patient materials. Human jejunal intestinal organoids derived from paediatric IF patients can be expanded efficiently in vitro with region-specific markers preserved after long-term culture. Decellularized human intestinal matrix with intact ultrastructure is used as biological scaffolds. Proteomic and Raman spectroscopic analyses reveal highly analogous biochemical composition of decellularized human SI and colon matrix, implying that they can both be utilised as scaffolds for jejunal graft reconstruction. Indeed, seeding of primary human jejunal organoids to either SI or colonic scaffolds in vitro can efficiently reconstruct functional jejunal grafts with persistent disaccharidase activity as early as 4 days after seeding, which can further survive and mature after transplantation in vivo. Our findings pave the way towards regenerative medicine for IF patients.