Decellularized Mouse Liver as a Small-Scale Scaffold for the Creation of a Miniaturized Human Liver

The liver is the main organ responsible for drug metabolism; hepatocyte-based culture models play a fundamental role in understanding physiology. While different types of two-dimensional and three-dimensional have been developed, failure to accurately mimic native liver, including extracellular matrix (ECM) composition, complex structure, rich vascular network as well shortage donors, impede their clinical translation. Herein, we realized “miniature human liver” based on infusion primary hepatocytes into decellularized template (DC-liver) made from right lobe mouse. We performed detergent-based decellularization mouse sections via portal vein (PV) perfusion confirmed successful removal cell content, preservation network. Subsequently, DC-liver templates were recellularized at varying densities, 3 × 106 1 107 cells/mL, specific gene expression was assessed. Overall, constructs (RC-liver) expressed liver-specific mRNA markers (Hnf4α, Alb) level comparable unseeded, freshly isolated seeded inside collagen gels. However, RC-liver with highest density exhibited poor distribution blockage PV, general, showed elevated levels Cyp1a1. Further analysis hinted hypoxic conditions constructs, showing higher hypoxia-related genes (Hif-1α, Casp3, Zo-1). Fortunately, oxygen supplementation appeared alleviate hypoxia, which markedly reduced Hif-1α Cyp1α1. As proof-of-concept, also templates, could confirm (HNF4A, ALB, CYP3A4). Altogether, above results indicate profound potential use tissue fabrication miniature may application prospects regenerative medicine, engineering (TE) other related disciplines.