Mesenchymal Stem Cell-Seeded Regenerated Silk Fibroin Complex Matrices for Liver Regeneration in an Animal Model of Acute Liver Failure.

Abstract

The main limitation of liver transplantation as a treatment for end-stage liver disease or acute liver failure is the scarcity of liver organ donors. To develop an alternative therapy for acute liver failure, mesenchymal stem cell (MSC)-seeded regenerated silk fibroin (RSF) matrices were evaluated in vitro and in vivo. Adipose-derived mesenchymal stem cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) were planted and grown on RSF scaffolds to form a scaffold complex. The RSF-MSC scaffold complex (the experimental group) and neat RSF scaffolds (the control group) were then placed onto the liver surface of mice induced by CCl4 and detected after 5, 7, 14, 28, and 60 days. The growth and distribution of MSCs were tracked using fluorescence microscopy and live small animal fluorescence. Liver functions were tested using an automatic biochemistry analyzer. The histological kinetics of RSF complex and liver tissues were observed using hematoxylin & eosin staining. We found that MSCs exhibited good biocompatibility with RSF and differentiated to hepatocyte-like cells in vitro. Liver functions of the mice in the experimental group were significantly improved than that in the control group. Moreover, angiogenesis and hepatocyte-like cells were discovered in the RSF scaffolds in an animal model of acute liver failure on the fifth day and in the second month, respectively. The MSCs-RSF matrices show an obvious therapeutic ability for injured liver function of mice, which is more efficient than the neat RSF scaffolds.