Overview

• The team differentiated human pluripotent stem cells into CD32b+ liver sinusoidal endothelial progenitors and used an inverted multilayered air-liquid interface culture to produce organoids that autonomously formed sinusoidal vessels.
• Advanced liver organoids generated four key coagulation factors, including Factor VIII, addressing the primary deficiency in hemophilia A.
• Organoid-derived Factor VIII restored normal clotting and rescued hemophilic mice from severe bleeding, demonstrating functional efficacy in vivo.
• Liver-specific progenitor cells offered enhanced compatibility and integration compared to non-organ-specific endothelial cells, improving vascular network formation.
• The breakthrough could lead to scalable sources of clotting proteins and pave the way for vascularized liver tissue therapies for hemophilia, liver failure and other coagulation disorders.