Acellular lung matrix scaffold coated by fibronectin enhances hepatic differentiation of adipose-derived mesenchymal stem cells.

End-stage liver disease is a multifactorial disorder and leading cause of death. The development of effective tissue models has been a focus of research for treating liver disease. This study investigated the use of acellular lung matrix (ALM) and fibronectin (FN) to culture adipose-derived mesenchymal stem cells (ADMSCs) and promote their differentiation into hepatic-like cells. In this experimental study, sodium deoxycholate and NaCl were used to decellularize the lungs, and scaffolds were characterized by histology, scanning electron microscopy, and DNA quantification. ADMSCs were differentiated into hepatocyte-like cells using a two-step protocol under three conditions: in two-dimensional culture, on ALM scaffolds, and on FN-coated ALM scaffolds. Hepatic differentiation was confirmed by RT-PCR for specific genes (alpha-fetoprotein [AFP], albumin [ALB], cytokeratin-18 [CK-18]), ALB and urea levels were measured using specific commercial kits. The main extracellular matrix components (collagen and glycosaminoglycans) were preserved, and residual DNA was minimal (P<0.001), indicating effective decellularization. ADMSCs cultured on FN-coated ALM exhibited significantly higher expression of hepatic markers (AFP, P<0.01; ALB, P<0.01; CK-18, P<0.01). Functional assay confirmed higher ALB and urea production (P<0.05), while MTT assay demonstrated that the scaffold was non-cytotoxic. Collectively, these results demonstrate that FN-coated ALM holds considerable potential for facilitating the hepatic differentiation of ADMSCs under the applied induction conditions.