Cell therapy for hemophilia A

Hemophilia A (HA) is a X-bleeding disorder caused by mutations in the FVIII gene, leading to deficient coagulation factor VIII activity. Current treatment entails repeated infusions of exogenous FVIII, which is frequently hampered by the formation of neutralising antibodies. This study investigates the efficacy of fetal liver (FL) and juvenile bone marrow (JBM) cells for HA cell therapy, with an emphasis on engraftment and FVIII production in neonatal and adult HA mice. We show that FL cells, particularly those from embryonic day (E) 13, can engraft and produce FVIII in HA newborn mice even without preconditioning, greatly improving the bleeding phenotype. Adult bone marrow (ABM) cells, on the other hand, require busulfan (BU) preconditioning in order to engraft and correct phenotypes in neonatal HA mice. Furthermore, we study the transplantation kinetics of JBM cells, finding that they outperform ABM cells in terms of engraftment, particularly in adult HA mice preconditioned with BU. Notably, the use of granulocyte colony-stimulating factor (G-CSF) as a mobilisation agent improves JBM cell engraftment, suggesting a feasible technique for reducing reliance on hazardous preconditioning regimens. These findings indicate FL and JBM cells as feasible sources for HSC transplantation in HA treatment, providing insights into their varying engraftment efficiencies and the function of mobilisation agents in improving transplantation outcomes. This study paves the way for new HA treatment techniques, highlighting the importance of cell source selection and mobilisation tactics in obtaining effective and long-term therapeutic effects.