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

iScience

Alice Maestri¹  Federico Scottoni²  Alessandro Filippo Pellegata²  Kevin Mills³  Soichi Shibuya³  Paul Gissen³  Asllan Gjinovci³  Elena Alvarez Mediavilla⁴  Wendy E. Heywood⁴  Daniel Kysh⁴  Paolo De Coppi⁴  Dany P. Perocheau⁵  Chiara Turchetta⁶  Tristan R. McKay⁶  Juliette M. Delhove⁶  John R. Counsell⁶  Andrei Claudiu Cozmescu⁷  Brendan Jones⁸  Maëlle Lorvellec⁸ 

[1] Corresponding author;Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK;Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK;;Teaching Department, Stem Cells &Department of Chemistry, Materials and Chemical Engineering ''Giulio Natta,'' Politecnico di Milano, Milan 20133, Italy;;Developmental Biology and Cancer Research &Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK;MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK;

关键词: Clinical Genetics;    Bioengineering;    Tissue Engineering;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown