Bioinspired Artificial Liver System with hiPSC-derived Hepatocytes for Acute Liver Failure Treatment.

Abstract

Bioartificial liver (BAL) system has become a promising alternative to traditional liver transplantation in rescuing acute liver failure (ALF) patients. Herein, inspired by natural microstructure of hepatic lobules, we developed a novel biomimetic bioartificial liver system (BBALS) by integrating human induced pluripotent stem cell-derived hepatocytes (hiPSC-Heps) cell-laden microparticles and semipermeable microtubes into a microfluidic platform. As the working units were hepatic lobules-like semipermeable microtubes surrounding with serum-free suspension differentiated hiPSC-Heps microcarriers, the BBALS was endowed with functional cell aggregates and effective circulation system. Thus, the BBALS possessed high cell viability, favorable function regeneration, and effective substances exchange. Based on these features, we created a three-dimensional (3D) liver chip with multiple parallel BBALS units for filtering the plasma of ALF rabbits, which validated the research significance and application potential of the proposed BBALS. Moreover, the novel integrated BBALS was applied to treat ALF rabbits and showed great advantages in increasing survival, generating serum proteins, and decreasing inflammation. These properties point to the broad prospects of BBALS in treating related diseases and improving traditional clinical methods. This article is protected by copyright. All rights reserved.