Histopathologic analysis of hematopoietic tissues in Hbb^+/+, Hbb^th3/+, and Hbb^th3/th3 chimeras.

(A) Bone marrow (original magnification, × 60). Left: Hbb^+/+ control. The marrow shows various stages of normal erythroid maturation. Megakaryocytes as well as a significant numbers of maturing myeloid cells are present. Center: Hbb^th3/+ control. The marrow shows a relative increase in erythroid elements; some myeloid cells are still present. Right: Hbb^th3/th3 chimera. Misshapen erythroid cells and red cell fragments are present in the sinuses. Some of the immature erythroid cells have dysmorphic nuclei. Mature erythroid cells are decreased. (B) Spleen (original magnification, × 60). Left: Hbb^+/+ control. The red pulp contains a mixture of erythroid and myeloid cells. The sinuses are open. Center: Hbb^th3/+ control. Significant expansion of red pulp compressing the sinuses. Right: Hbb^th3/th3 chimera. The red pulp consists primarily of immature erythroid cells. Mitotic figures are easily identified. The immature erythroid cells often have abnormal nuclei. (C) Liver (original magnification, × 20). Left: Hbb^+/+ control. EMH is absent. Center: Hbb^th3/+ control. Moderate EMH is present. Right: Hbb^th3/th3 chimera: Extensive EMH is present. (D) Liver (original magnification, × 20), Gomori stain). Left: Hbb^+/+ control: undetectable iron. Center: Hbb^th3/+ control. Moderate iron deposits predominantly in Kuppfer cells. Right: Hbb^th3/th3 chimera: Diffuse iron accumulation, concentrated in the cytoplasm of the hepatocytes preferentially around the portal tracts. Control tissues from mice engrafted with eGFP-transduced Hbb^+/+ or Hbb^th3/+ FLCs were harvested 6 and 8 months after transplantation. Tissues from control Hbb^th3/th3 chimeras were harvested 8 weeks after transplantation. Stained with hematoxylin and eosin (A-C).