期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-06385-w
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资金
- National Institute for Health Research [NIHR-RP-2014-04-046]
- NIHR
- OAK Foundation [W1095/OCAY-14-191]
- Great Ormond Street Hospital (GOSH) Children's Charity
- UCL Excellence Fellowship Programme
- Rosetrees Trust [M362, M553]
- NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust
- MRC [MR/P016006/1]
- NIHR GOSH BRC award [17DD08]
- UCL Grand Challenge Studentship
- UK Stem Cell Foundation
- Cell and Gene Therapy Catapult
- GOSH Charity [V1282]
- OAK Foundation
- MRC [MR/P016006/1] Funding Source: UKRI
- Rosetrees Trust [M362, M553, M362-F1] Funding Source: researchfish
A tissue engineered oesophagus could overcome limitations associated with oesophageal substitution. Combining decellularized scaffolds with patient-derived cells shows promise for regeneration of tissue defects. In this proof-of-principle study, a two-stage approach for generation of a bio-artificial oesophageal graft addresses some major challenges in organ engineering, namely: (i) development of multi-strata tubular structures, (ii) appropriate repopulation/maturation of constructs before transplantation, (iii) cryopreservation of bio-engineered organs and (iv) in vivo pre-vascularization. The graft comprises decellularized rat oesophagus homogeneously re-populated with mesoangioblasts and fibroblasts for the muscle layer. The oesophageal muscle reaches organised maturation after dynamic culture in a bioreactor and functional integration with neural crest stem cells. Grafts are pre-vascularised in vivo in the omentum prior to mucosa reconstitution with expanded epithelial progenitors. Overall, our optimised two-stage approach produces a fully re-populated, structurally organized and pre-vascularized oesophageal substitute, which could become an alternative to current oesophageal substitutes.
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