Engineering transplantable jejunal mucosal grafts using primary patient-derived organoids from children with intestinal failure
| Autor: | Paola Bonfanti, Anna Baulies, Vivian S. W. Li, Nikhil Thapar, P De Coppi, L Meran, Ambrosius P. Snijders, Michael Orford, Anna Kucharska, Riana Gaifulina, Simon Eaton, Elizabeth M. A. Hirst, Geraint M.H. Thomas, Lucy M. Collinson, Isobel Massie, S. Eli, Julia König, Anne Weston, Peter Faull, Alfonso M Tedeschi, Alessandro Filippo Pellegata |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Pathology medicine.medical_specialty Decellularization business.industry food and beverages Regenerative medicine Small intestine Disaccharidase 3. Good health Transplantation Jejunum 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure In vivo 030220 oncology & carcinogenesis Organoid medicine business 030304 developmental biology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|