Development of 3D Hepatic Constructs Within Polysaccharide-Based Scaffolds with Tunable Properties.

Autor: Labour MN; INSERM U1148, LVTS, Université de Paris, X Bichat Hospital, 46 rue H Huchard, F-75018 Paris, France.; INSERM U1148, LVTS, Université Sorbonne Paris Nord, 99 av JB Clément, 93430 Villetaneuse, France.; École Pratique des Hautes Études, Paris Sciences et Lettres (PSL) Research University, 4-14 rue Ferrus, 75014 Paris, France., Le Guilcher C; INSERM U1148, LVTS, Université de Paris, X Bichat Hospital, 46 rue H Huchard, F-75018 Paris, France.; INSERM U1148, LVTS, Université Sorbonne Paris Nord, 99 av JB Clément, 93430 Villetaneuse, France., Aid-Launais R; INSERM U1148, LVTS, Université de Paris, X Bichat Hospital, 46 rue H Huchard, F-75018 Paris, France.; INSERM UMS-34, FRIM Université de Paris, X Bichat School of Medicine, F-75018 Paris, France., El Samad N; INSERM U1148, LVTS, Université de Paris, X Bichat Hospital, 46 rue H Huchard, F-75018 Paris, France.; INSERM U1148, LVTS, Université Sorbonne Paris Nord, 99 av JB Clément, 93430 Villetaneuse, France., Lanouar S; INSERM U1148, LVTS, Université de Paris, X Bichat Hospital, 46 rue H Huchard, F-75018 Paris, France.; INSERM U1148, LVTS, Université Sorbonne Paris Nord, 99 av JB Clément, 93430 Villetaneuse, France., Simon-Yarza T; INSERM U1148, LVTS, Université de Paris, X Bichat Hospital, 46 rue H Huchard, F-75018 Paris, France.; INSERM U1148, LVTS, Université Sorbonne Paris Nord, 99 av JB Clément, 93430 Villetaneuse, France., Letourneur D; INSERM U1148, LVTS, Université de Paris, X Bichat Hospital, 46 rue H Huchard, F-75018 Paris, France.; INSERM U1148, LVTS, Université Sorbonne Paris Nord, 99 av JB Clément, 93430 Villetaneuse, France.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2020 May 21; Vol. 21 (10). Date of Electronic Publication: 2020 May 21.
DOI: 10.3390/ijms21103644
Abstrakt: Organoids production is a key tool for in vitro studies of physiopathological conditions, drug-induced toxicity assays, and for a potential use in regenerative medicine. Hence, it prompted studies on hepatic organoids and liver regeneration. Numerous attempts to produce hepatic constructs had often limited success due to a lack of viability or functionality. Moreover, most products could not be translated for clinical studies. The aim of this study was to develop functional and viable hepatic constructs using a 3D porous scaffold with an adjustable structure, devoid of any animal component, that could also be used as an in vivo implantable system. We used a combination of pharmaceutical grade pullulan and dextran with different porogen formulations to form crosslinked scaffolds with macroporosity ranging from 30 µm to several hundreds of microns. Polysaccharide scaffolds were easy to prepare and to handle, and allowed confocal observations thanks to their transparency. A simple seeding method allowed a rapid impregnation of the scaffolds with HepG2 cells and a homogeneous cell distribution within the scaffolds. Cells were viable over seven days and form spheroids of various geometries and sizes. Cells in 3D express hepatic markers albumin, HNF4α and CYP3A4, start to polarize and were sensitive to acetaminophen in a concentration-dependant manner. Therefore, this study depicts a proof of concept for organoid production in 3D scaffolds that could be prepared under GMP conditions for reliable drug-induced toxicity studies and for liver tissue engineering.
Databáze: MEDLINE
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