F8 and severe combined immunodeficiency: When ECFCs were engineered with non-viral plasmids encoding for human coagulation factor VIII (FVIII), they mainly engrafted within the bone marrow and spleen of NOD/SCID (non-obese diabetes/severe combined immunodeficiency) mice and retained both transgene expression and the endothelial phenotype; in addition, they persisted in secreting in circulation therapeutic levels of FVIII even at 5 months after transplantation [217].