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4 results on '"Soichi Shibuya"'

1. Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model

Author

Edward Hannon, Marco Pellegrini, Federico Scottoni, Natalie Durkin, Soichi Shibuya, Roberto Lutman, Toby J. Proctor, J. Ciaran Hutchinson, Owen J. Arthurs, Demetra-Ellie Phylactopoulos, Elizabeth F. Maughan, Colin R. Butler, Simon Eaton, Mark W. Lowdell, Paola Bonfanti, Luca Urbani, and Paolo De Coppi

Subjects
Biological sciences, Biomedical engineering, Tissue engineering, Biotechnology, Science
Abstract

Summary: Decellularization of esophagi from several species for tissue engineering is well described, but successful implantation in animal models of esophageal replacement has been challenging. The purpose of this study was to assess feasibility and applicability of esophageal replacement using decellularized porcine esophageal scaffolds in a new pre-clinical model. Following surgical replacement in rabbits with a vascularizing muscle flap, we observed successful anastomoses of decellularized scaffolds, cues of early neovascularization, and prevention of luminal collapse by the use of biodegradable stents. However, despite the success of the surgical procedure, the long-term survival was limited by the fragility of the animal model. Our results indicate that transplantation of a decellularized porcine scaffold is possible and vascular flaps may be useful to provide a vascular supply, but long-term outcomes require further pre-clinical testing in a different large animal model.

Published
2022
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2. An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies

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, and Paul Gissen

Subjects
Clinical Genetics, Bioengineering, Tissue Engineering, Science
Abstract

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.

Published
2020
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3. An

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, and Paul, Gissen

Subjects
Clinical Genetics, Tissue Engineering, Bioengineering, Article
Abstract

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., Graphical Abstract, Highlights • Generation of a perfused humanized in vitro whole liver bioreactor model: BALM • BALM improves maturation and long-term survival of human iPS-derived hepatocytes • BALM allows viral transduction of human iHEPs through its vasculature • BALM provides a tool for gene therapy testing of human iHEPs, Clinical Genetics; Bioengineering; Tissue Engineering

Published
2020

4. An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies

Author

Asllan Gjinovci, Dany P. Perocheau, Paolo De Coppi, Maëlle Lorvellec, Federico Scottoni, Daniel Kysh, Alice Maestri, Tristan R. McKay, Paul Gissen, Kevin Mills, Chiara Turchetta, Soichi Shibuya, Wendy E. Heywood, Elena Alvarez Mediavilla, Juliette M. K. M. Delhove, Alessandro Filippo Pellegata, Andrei Claudiu Cozmescu, Brendan C. Jones, and John R. Counsell

Subjects
0301 basic medicine, ALPHA-FETOPROTEIN, Transgene, Genetic enhancement, Cell, RAT-LIVER, Bioengineering, 02 engineering and technology, Biology, TRANSDUCTION, VIVO, 03 medical and health sciences, Transduction (genetics), Tissue engineering, medicine, lcsh:Science, Induced pluripotent stem cell, Clinical Genetics, Science & Technology, Multidisciplinary, Decellularization, Tissue Engineering, HEMOPHILIA, FACTOR-IX, 021001 nanoscience & nanotechnology, HEPATOCYTE-LIKE CELLS, In vitro, 3. Good health, Multidisciplinary Sciences, 030104 developmental biology, medicine.anatomical_structure, DRUG-METABOLISM, SAFETY, INTRACELLULAR PH, Cancer research, Science & Technology - Other Topics, lcsh:Q, 0210 nano-technology
Abstract

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. ispartof: ISCIENCE vol:23 issue:12 ispartof: location:United States status: published

Published
2020

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