Fetal liver haemato/vascular progenitor cells as a cell based therapeutic tool for neonatal haemophilia

Resumen del trabajo presentado en el 27th ESGCT Annual Congress in collaboration with SETGyc, celebrado en Barcelona (España), del 22 al 25 de octubre de 2019
The development of strategies based on cell therapy approaches requires further insights into new stem/progenitor cell populations presenting stable engraftment potential and restoration capacity of the deficient factors causing the disease. We have previously shown that hemato/vascular progenitor cells from the foetal liver (FL) possess higher hematopoietic and vascular endothelial engraftment potential when transplanted to newborn mice compared with adult-derived counterpart progenitor cells (1), constituting likely therapeutic targets for the treatment of congenital hemato/vascular related diseases in neonates. The hemophilia A (HA, a deficiency of factor FVIII) and other rare coagulation disorders, including deficiency of factor FV, are caused by mutations decreasing the production of coagulation factors by hematopoietic and/or vascular endothelial cells. We have shown that different FL-derived cell populations produce FVIII (2), suggesting its suitability as cell therapeutic targets for the treatment of hemophilia diseases. Here we will present the results on the phenotypic and functional characterization of FL progenitors, focusing in three aspects: 1) Characterization of vascular endothelial stem cells during development; 2) Determination of coagulation factor production; 3) Analysis of chimeric HA mice transplanted with wild type FLGFP-derived cells at day 1 after birth. These research should be instrumental for the establishment of a preclinical model for HA treatment in neonates. (1) Cañete el all, Stem Cells, 2017. doi.org/10.1002/stem.2494 (2) Serrano et al, Throm & Haem, 2018. doi.org/10.1055/s-0038-1661351