A minimally-invasive cryogel based approach for the development of human ectopic liver in a mouse model.

Abstract

Human liver tissue is preferable over nonhuman liver tissue for preclinical drug screening, as the former can better predict side effects specific to humans. However, due to limited supply and ethical issues with human liver tissue, it is desirable to develop an animal model having functional human liver tissue. In this study, we have established an ectopic functional human liver tissue in a mouse model, using a minimally-invasive method. Firstly, a human liver tissue mass using HepG2 cells and poly(N-isopropylacrylamide) (PNIPAAm) incorporated poly(ethylene glycol)-alginate-gelatin (PAG) cryogel matrix was developed in vitro. It was later implanted in mouse peritoneal cavity using a 16 G needle. Viscoelastic nature along with low Young's modulus provided injectable properties to the cryogel. We confirmed minimal cell loss/death while injecting. Further, by in vivo study efficacy of both injectable and surgical implantation approaches were compared. No significant difference in terms of cell infiltration, human serum albumin (HSA) secretion and enzyme activity confirmed efficacy. This model developed using a minimally-invasive approach can overcome the limitations of surgical implantation due to its cost effective and user friendly nature.