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 beta-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 beta-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<