An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies
| Autor: | 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, John R. Counsell |
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| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | iScience, Vol 23, Iss 12, Pp 101808-(2020) |
| ISSN: | 2589-0042 |
| DOI: | 10.1016/j.isci.2020.101808 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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