Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors

被引：69

作者：

Urbani, Luca ^{[1
,2
]}

Camilli, Carlotta ^{[1
]}

Phylactopoulos, Demetra-Ellie ^{[1
,3
]}

Crowley, Claire ^{[1
]}

Natarajan, Dipa ^{[1
]}

Scottoni, Federico ^{[1
]}

Maghsoudlou, Panayiotis ^{[1
]}

McCann, Conor J. ^{[1
]}

Pellegata, Alessandro Filippo ^{[1
]}

Urciuolo, Anna ^{[1
]}

Deguchi, Koichi ^{[1
]}

Khalaf, Sahira ^{[1
]}

Aruta, Salvatore Ferdinando ^{[1
]}

Signorelli, Maria Cristina ^{[1
]}

Kiely, David ^{[1
]}

Hannon, Edward ^{[1
]}

Trevisan, Matteo ^{[1
]}

Wong, Rui Rachel ^{[1
]}

Baradez, Marc Olivier ^{[4
]}

Moulding, Dale ^{[1
]}

Virasami, Alex ^{[5
]}

Gjinovci, Asllan ^{[1
]}

Loukogeorgakis, Stavros ^{[1
]}

Mantero, Sara ^{[6
]}

Thapar, Nikhil ^{[1
]}

Sebire, Neil ^{[1
]}

Eaton, Simon ^{[1
]}

Lowdell, Mark ^{[7
,8
]}

Cossu, Giulio ^{[9
]}

Bonfanti, Paola ^{[1
,3
,7
,8
]}

De Coppi, Paolo ^{[1
,10
]}

机构：

[1] UCL, Great Ormond St Inst Child Hlth, Stem Cell & Regenerat Med Sect, London WC1N 1EH, England

[2] Fdn Liver Res, Inst Hepatol, London SE5 9NT, England

[3] Francis Crick Inst, London NW1 1AT, England

[4] Cell & Gene Therapy Catapult, London SE1 9RT, England

[5] UCL, Great Ormond St Hosp, Dept Histopathol, London WC1N 3JH, England

[6] Politecn Milan, Dept Chem Mat & Chem Engn Giulio Natta, I-20133 Milan, Italy

[7] Royal Free London NHS FT, London NW3 2QG, England

[8] UCL, London NW3 2QG, England

[9] Univ Manchester, Manchester Acad Hlth Ctr, Div Cell Matrix & Regenerat Med, Manchester, Lancs, England

[10] Great Ormond St Hosp Sick Children, Specialist Neonatal & Paediat Unit, London WC1N 1EH, England

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

DETERGENT ENZYMATIC TREATMENT; SMALL-INTESTINAL SUBMUCOSA; MULTIPOTENT STEM-CELLS; EXTRACELLULAR-MATRIX; ACELLULAR MATRIX; SKELETAL-MUSCLE; CANINE MODEL; BIOLOGIC SCAFFOLDS; DOG-MODEL; TISSUE;

D O I：

10.1038/s41467-018-06385-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

共 67 条

[1] Resorbable bioscaffold for esophageal repair in a dog model [J].