Control and CA mouse histopathological features before and after transplantation. (A) Peripheral blood smears and histopathological features of spleen and liver sections of humanized HbA control, nontransplanted CA, and transplanted CA mice. The morphological status of RBCs in the blood of nontransplanted CA mice shows marked anisopoikilocytosis and hypochromia with numerous nucleated RBCs. In contrast, the blood of transplanted CA mice is normocytic and normochromic, similar to the nonanemic HbA control mice. Nontransplanted CA mice have splenomegaly with a massive expansion of erythroid progenitors, whereas the spleens of transplanted CA mice are normalized, similar to HbA control mice. There is marked extramedullary hematopoiesis and excess iron in the livers of nontransplanted CA mice. After transplantation the livers of CA mice are normalized, similar to control mice. Scale bar is 5 μm for the blood, 50 μm for the spleen, 25 μm for the liver (low power), 5 μm for the liver (high power), and 25 μm for the liver iron stain. (B) Histological sections of the intestine, skin, and lung of wild-type control and transplanted CA mice were examined for evidence of GVHD. Five months after transplantation, the skin, intestine, and lung were fixed and stained with hematoxylin and eosin. No GVHD was observed in CA mice after BMT in the absence of cytoreductive conditioning. Scale bar is 100 μm for the intestine and 50 μm for the lung and skin.