Development of hepatic blocks using human adipose tissue-derived stem cells through three-dimensional cell printing techniques

Abstract

Currently, most acute liver diseases are treated through liver transplantation. However, transplantation is limited by organ donor scarcity and immune rejection response. Moreover, only three types of commercial bio-artificial livers are available, and these have marginal effects on survival rates. Therefore, tissue regenerative medicine using stem cells has been developed to solve such unmet medical needs. In this study, we attempted to differentiate human adipose stem cells (hASCs) into hepatocyte-like cells (AHLCs) and fabricate liver regenerative hepatic block scaffolds, consisting of only hASCs and AHLCs, through three-dimensional cell printing using a neutralized type I atelo collagen solution derived from porcine skin. Hepatic blocks were also treated with genipin, a natural cross-linking reagent, in order to maintain the structure and strength of collagen scaffolds, which contained hASCs and AHLCs. The hepatic blocks were then transplanted into the livers of SD rats to confirm safety and efficiency. The results showed that hASCs and AHLCs inside the hepatic blocks translocated into the portal vein of hepatic lobules in SD rats by 4 weeks after transplantation, as demonstrated by immunohistochemical staining using human nuclear-specific antibodies. Moreover, serum biochemistry, which was altered after induction of acute liver failure by dimethylnitrosamine, returned to normal in hASC scaffold-transplanted rats, and increased levels of interleukin-10 expression were observed in the livers of these rats. Thus, these hepatic blocks consisting of hASCs could be used as alternative bio-artificial livers to facilitate the regeneration of damaged liver tissue.