Engineering transplantable jejunal mucosal grafts using primary patient-derived organoids from children with intestinal failure
Engineering transplantable jejunal mucosal grafts using primary patient-derived organoids from children with intestinal failure
Abstract 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.
Thomas Geriant、Weston Anne、Li Vivian S.W.、Meran Laween、Gaifulina Riana、Orford Michael、Kucharska Anna、Konig Julia、Collinson Lucy、Tedeschi Alfonso Maria、Massie Isobel、De Coppi Paolo、Pellegata Alessandro Filippo、Thapar Nikhil、Eaton Simon、Baulies Anna、Bonfanti Paola、Snijders Ambrosius P.、Eli Susanna、Hirst Elizabeth、Faull Peter
Department of Cell and Developmental Biology, University College LondonStem Cell and Cancer Biology Lab, The Francis Crick InstituteStem Cell and Cancer Biology Lab, The Francis Crick InstituteStem Cell and Cancer Biology Lab, The Francis Crick Institute||Stem Cell and Regenerative Medicine Section, DBC, Great Ormond Street Institute of Child Health, University College of LondonDepartment of Cell and Developmental Biology, University College LondonStem Cell and Regenerative Medicine Section, DBC, Great Ormond Street Institute of Child Health, University College of LondonStem Cell and Cancer Biology Lab, The Francis Crick InstituteStem Cell and Cancer Biology Lab, The Francis Crick InstituteStem Cell and Cancer Biology Lab, The Francis Crick InstituteStem Cell and Regenerative Medicine Section, DBC, Great Ormond Street Institute of Child Health, University College of LondonStem Cell and Cancer Biology Lab, The Francis Crick InstituteStem Cell and Regenerative Medicine Section, DBC, Great Ormond Street Institute of Child Health, University College of LondonStem Cell and Regenerative Medicine Section, DBC, Great Ormond Street Institute of Child Health, University College of LondonStem Cell and Regenerative Medicine Section, DBC, Great Ormond Street Institute of Child Health, University College of LondonStem Cell and Regenerative Medicine Section, DBC, Great Ormond Street Institute of Child Health, University College of LondonStem Cell and Cancer Biology Lab, The Francis Crick InstituteStem Cell and Cancer Biology Lab, The Francis Crick Institute||Stem Cell and Regenerative Medicine Section, DBC, Great Ormond Street Institute of Child Health, University College of LondonStem Cell and Cancer Biology Lab, The Francis Crick InstituteStem Cell and Regenerative Medicine Section, DBC, Great Ormond Street Institute of Child Health, University College of LondonStem Cell and Cancer Biology Lab, The Francis Crick InstituteStem Cell and Cancer Biology Lab, The Francis Crick Institute
生物工程学基础医学医学研究方法
Thomas Geriant,Weston Anne,Li Vivian S.W.,Meran Laween,Gaifulina Riana,Orford Michael,Kucharska Anna,Konig Julia,Collinson Lucy,Tedeschi Alfonso Maria,Massie Isobel,De Coppi Paolo,Pellegata Alessandro Filippo,Thapar Nikhil,Eaton Simon,Baulies Anna,Bonfanti Paola,Snijders Ambrosius P.,Eli Susanna,Hirst Elizabeth,Faull Peter.Engineering transplantable jejunal mucosal grafts using primary patient-derived organoids from children with intestinal failure[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/854083.点此复制
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