Background : Biliary complications represent a significant challenge following living-donor liver transplantation (LDLP), with an incidence rate of up to 25%. Among these complications, Biliary stricture leads to digestive issues, jaundice, and abdominal discomfort. Current treatments for biliary stricture, such as endoscopic therapy and stent placement, are constrained by limitations in reach, visibility, and temporally efficacy. This study proposes a solution employing 3D Y-shaped silicone stents coated with human chemically derived hepatic progenitors (hCdHs) to overcome these limitations.

Methods : The generation of hCdHs involved the treatment of HGF, CHIR99021, and A83-01 compounds from human primary hepatocytes (hPHs) isolated from the human liver. These hCdHs were seeded onto silicone stents and underwent a 14-day differentiation into cholangiocytes. Immunofluorescence staining confirmed the presence of hCdH-cholangiocytes (hCdH-Chols) on the stents, and qPCR analysis identified cholangiocyte differentiation markers.

Results : Immunofluorescence images demonstrated an increase in cell population of hCdH-Chols as hCdHs differentiated. Furthermore, PCR results showed a significant upregulation in cholangiocyte marker gene expression of hCdH-Chols on the stent compared to hCdHs, resembling or surpassing the expression levels in hCdH-Chols cultured in 2D environment.

Conclusions : This study highlights the successful differentiation of hCdHs into cholangiocytes on silicone stents. These results suggest a promising patient-specific therapeutic strategy in treatment of biliary tract diseases.