Transplantation of KLF1-GATA1–expressing SCD mouse HSCs into SCD mice reduces the percent of sickling cells in peripheral blood and improves SCD-related pathologic changes in spleen, kidney, and liver. Mock- or KLF1-GATA1–transduced SCD mouse HSCs were transplanted into SCD mice. Recipient mice were euthanized 20 to 24 weeks after transplantation, and peripheral blood and tissues were collected. Tissue sections were stained to evaluate organ pathology and iron accumulation. (A) Representative Giemsa staining of peripheral blood smear for evaluating erythrocyte morphology. Bar represents 20 μm. Images were acquired with an Olympus BX51 microscope (Olympus, Center Valley, PA) and a Qimaging Camera with Q Capture pro software (Qimaging, Surrey, BC, Canada). Four random fields were imaged from each sample, and cellular morphologies were scored by blinded observers. ∗∗P < .01 vs vector control–transduced cells. Error bars indicate the mean ± SD results of 3 independent experiments. (B) Representative spleen tissue stained with hematoxylin and eosin (H&E). Bars represent 50 μm. (C) Top row: representative kidney tissue stained with H&E. Bar represents 50 μm. Middle and bottom rows: representative kidney tissue stained with Prussian blue for iron content. Bar represents 100 μm (middle) and 20 μm (bottom). (D) Representative liver sections stained with Prussian blue for iron content. Bar represents 50 μm. (E) Representative spleens collected from recipient mice. Mock mice are SCD mice with mock-transduced SCD mouse HSC transplants; KG-M and KG-L mice are SCD mice that receive transplants of medium- and long-form KLF1-GATA1–transduced SCD mouse HSCs, respectively.