“…5 On the other hand, transplantation of liver from hemophilic donors, either dogs 6 or humans, 7 into healthy subjects does not cause hemophilia, indicating that FVIII is also produced in extrahepatic sites. Recent studies using a cell therapy approach 8,9 or cell typespecific knockout experiments indicated that FVIII is produced largely in liver sinusoidal endothelial cells (LSEC); 10,11 although FVIII mRNA was present in endothelial cells of kidneys, spleen and lungs, it was absent in endothelial cells of the brain and heart. 10,[12][13][14][15] These findings were in agreement with studies showing that hemophilic patients benefited from transplantation of the spleen in the long-term.…”