An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies
Summary: Explosion of gene therapy approaches for treating rare monogenic and common liver disorders created an urgent need for disease models able to replicate human liver cellular environment. Available models lack 3D liver structure or are unable to survive in long-term culture. We aimed to gener...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220310051 |
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doaj-c043e3e17edd419a9dda615cee1a696f |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Maëlle Lorvellec Alessandro Filippo Pellegata Alice Maestri Chiara Turchetta Elena Alvarez Mediavilla Soichi Shibuya Brendan Jones Federico Scottoni Dany P. Perocheau Andrei Claudiu Cozmescu Juliette M. Delhove Daniel Kysh Asllan Gjinovci John R. Counsell Wendy E. Heywood Kevin Mills Tristan R. McKay Paolo De Coppi Paul Gissen |
| spellingShingle |
Maëlle Lorvellec Alessandro Filippo Pellegata Alice Maestri Chiara Turchetta Elena Alvarez Mediavilla Soichi Shibuya Brendan Jones Federico Scottoni Dany P. Perocheau Andrei Claudiu Cozmescu Juliette M. Delhove Daniel Kysh Asllan Gjinovci John R. Counsell Wendy E. Heywood Kevin Mills Tristan R. McKay Paolo De Coppi Paul Gissen An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies iScience Clinical Genetics Bioengineering Tissue Engineering |
| author_facet |
Maëlle Lorvellec Alessandro Filippo Pellegata Alice Maestri Chiara Turchetta Elena Alvarez Mediavilla Soichi Shibuya Brendan Jones Federico Scottoni Dany P. Perocheau Andrei Claudiu Cozmescu Juliette M. Delhove Daniel Kysh Asllan Gjinovci John R. Counsell Wendy E. Heywood Kevin Mills Tristan R. McKay Paolo De Coppi Paul Gissen |
| author_sort |
Maëlle Lorvellec |
| title |
An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies |
| title_short |
An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies |
| title_full |
An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies |
| title_fullStr |
An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies |
| title_full_unstemmed |
An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies |
| title_sort |
in vitro whole-organ liver engineering for testing of genetic therapies |
| publisher |
Elsevier |
| series |
iScience |
| issn |
2589-0042 |
| publishDate |
2020-12-01 |
| description |
Summary: Explosion of gene therapy approaches for treating rare monogenic and common liver disorders created an urgent need for disease models able to replicate human liver cellular environment. Available models lack 3D liver structure or are unable to survive in long-term culture. We aimed to generate and test a 3D culture system that allows long-term maintenance of human liver cell characteristics.The in vitro whole-organ “Bioreactor grown Artificial Liver Model” (BALM) employs a custom-designed bioreactor for long-term 3D culture of human induced pluripotent stem cells-derived hepatocyte-like cells (hiHEPs) in a mouse decellularized liver scaffold. Adeno-associated viral (AAV) and lentiviral (LV) vectors were introduced by intravascular injection.Substantial AAV and LV transgene expression in the BALM-grown hiHEPs was detected. Measurement of secreted proteins in the media allowed non-invasive monitoring of the system.We demonstrated that humanized whole-organ BALM is a valuable tool to generate pre-clinical data for investigational medicinal products. |
| topic |
Clinical Genetics Bioengineering Tissue Engineering |
| url |
http://www.sciencedirect.com/science/article/pii/S2589004220310051 |
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doaj-c043e3e17edd419a9dda615cee1a696f2020-12-19T05:09:58ZengElsevieriScience2589-00422020-12-012312101808An In Vitro Whole-Organ Liver Engineering for Testing of Genetic TherapiesMaëlle Lorvellec0Alessandro Filippo Pellegata1Alice Maestri2Chiara Turchetta3Elena Alvarez Mediavilla4Soichi Shibuya5Brendan Jones6Federico Scottoni7Dany P. Perocheau8Andrei Claudiu Cozmescu9Juliette M. Delhove10Daniel Kysh11Asllan Gjinovci12John R. Counsell13Wendy E. Heywood14Kevin Mills15Tristan R. McKay16Paolo De Coppi17Paul Gissen18MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK; Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK; Corresponding authorDevelopmental Biology and Cancer Research & Teaching Department, Stem Cells & Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKMRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK; Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKDepartment of Chemistry, Materials and Chemical Engineering ''Giulio Natta,'' Politecnico di Milano, Milan 20133, ItalyGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKDevelopmental Biology and Cancer Research & Teaching Department, Stem Cells & Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKDevelopmental Biology and Cancer Research & Teaching Department, Stem Cells & Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKDevelopmental Biology and Cancer Research & Teaching Department, Stem Cells & Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKMRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London WC1N 1EH, UKRobinson Research Institute, University of Adelaide, Adelaide, SA, 5006, AustraliaMRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UKMRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UKDubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UKGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKGenetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKCentre for Bioscience, Manchester Metropolitan University, Manchester M1 5GD, UKDevelopmental Biology and Cancer Research & Teaching Department, Stem Cells & Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKMRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK; Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UKSummary: Explosion of gene therapy approaches for treating rare monogenic and common liver disorders created an urgent need for disease models able to replicate human liver cellular environment. Available models lack 3D liver structure or are unable to survive in long-term culture. We aimed to generate and test a 3D culture system that allows long-term maintenance of human liver cell characteristics.The in vitro whole-organ “Bioreactor grown Artificial Liver Model” (BALM) employs a custom-designed bioreactor for long-term 3D culture of human induced pluripotent stem cells-derived hepatocyte-like cells (hiHEPs) in a mouse decellularized liver scaffold. Adeno-associated viral (AAV) and lentiviral (LV) vectors were introduced by intravascular injection.Substantial AAV and LV transgene expression in the BALM-grown hiHEPs was detected. Measurement of secreted proteins in the media allowed non-invasive monitoring of the system.We demonstrated that humanized whole-organ BALM is a valuable tool to generate pre-clinical data for investigational medicinal products.http://www.sciencedirect.com/science/article/pii/S2589004220310051Clinical GeneticsBioengineeringTissue Engineering |