Modulating Liver Sinusoidal Endothelial Cell Permeability to Enhance Engraftment of Endothelial Cell Progenitors for the Treatment of Hemophilia A

Research was conducted into the transplantation of liver-derived endothelial cells for the treatment of hemophilia A.  Methods for the isolation of these cells and their expansion in culture were improved.  Engraftment of endothelial cells derived from fetal liver was shown in three different mouse models varying in the degree of liver damage.  As mice with undamaged livers engrafted, the general feasibility of the approach was demonstrated in an animal model.  The main hypothesis of the project was that pre-treatment with factors such VEGF which affect the permeability, or stickiness, of endothelial  cells to each other would enhance the engraftment of transplanted cells.  We did not observe this, as the pretreatment did not appear to have any effect on the engraftment of endothelial cells.  Although these results are discouraging, the basic finding that liver endothelial cells can be transplanted leading to engraftment in the liver in the absence of any chemical treatment is remarkable and encourages further effort at optimizing this approach to treat severe hemophilia A.