Experimental Correction and Treatment of Chronic Liver Failure Using Implantable Cell-Engineering Constructs of the Auxiliary Liver Based on a Bioactive Heterogeneous Biopolymer Hydrogel

Abstract

Our study sought approaches for chronic liver failure (CLF) treatment and correction via cell-engineered constructs (CECs). They are built from biopolymer-based, microstructured, and collagen-containing hydrogel (BMCG). We also strove to evaluate the functional activity of BMCG in liver regeneration. Materials and Methods: Allogeneic liver cells (namely, hepatocytes; LC) together with mesenchymal multipotent stem cells of bone marrow origin (MMSC BM; BMSCs) were adhered to our BMCG to compose implanted liver CECs. Thereafter, we investigated a model of CLF in rats receiving the implanted CECs. The CLF had been provoked by long-term exposure to carbon tetrachloride. The study comprised male Wistar rats (n = 120) randomized into 3 groups: Group 1 was a control group with the saline treatment of the hepatic parenchyma (n = 40); Group 2 received BMCG only (n = 40); and Group 3 was loaded with CECs implanted into the parenchyma of their livers (n = 40). August rats (n = 30) made up a donor population for LCs and MMSC BM to develop grafts for animals from Group 3. The study length was 90 days. Results: CECs were shown to affect both biochemical test values and morphological parameters in rats with CLF. Conclusion: We found BMCG-derived CECs to be operational and active, with regenerative potential. Group 3 showed significant evidence of forced liver regeneration that tended to persist until the end of the study (day 90). The phenomenon is reflected by biochemical signs of hepatic functional recovery by day 30 after grafting (compared to Groups 1 and 2), whereas structural features of liver repair (necrosis prevention, missing formation of vacuoles, degenerating LC number decrease, and delay of hepatic fibrotic transformation). Such implantation of BMCG-derived CECs with allogeneic LCs and MMSC BM might represent a proper option to correct and treat CLF, as well as to maintain affected liver function in patients with liver grafting needed.