Mixed chimerism following in utero hematopoietic stem cell transplantation in murine models of hemoglobinopathy

Objective Mixed hematopoietic chimerism after bone marrow transplantation can provide effective treatment for β-thalassemia because of the selective advantage that exists for donor erythropoiesis. In utero hematopoietic stem cell transplantation (IUHSCTx) can achieve mixed hematopoietic chimerism, particularly when a selective advantage exists for donor cells. To investigate the biology of IUHSCTx in hemoglobinopathies, we performed fully allogeneic IUHSCTx in murine models of β-thalassemia (Thal) and sickle cell disease (SCD). Materials and Methods We serially assessed and compared levels of mononuclear cell (MNC) and erythroid chimerism after IUHSCTx of either adult bone marrow (BM)- or fetal liver (FL)-derived allogeneic donor cells in the two hemoglobinopathy models, which differ significantly in their degree of anemia (Thal>>SCD) and red cell half-life (Thal<