FIG. 7.
Engraftment of CAR-transduced human HSPCs in humanized NSG mice. (a) Human engraftment (detected by the percentage of human CD45-positive cells) and CAR-positive cells shown as percentage of total harvested cells from bone marrows, spleens, and PB from humanized NSG mice 32 weeks postintrahepatic injection into pups. Mice were engrafted with nontransduced human HSPCs (NT) or CAR-transduced human HSPCs (CD19R or CD19RCD28). Values represent arithmetic means of results from three experiments with 2–7 mice per group and error bars represent mean+SEM. (b) Distribution of different human hematopoietic lineages in humanized mice, myeloid cells (CD33+), B-lymphocytes (CD19+), T-lymphocytes (CD3+), and NK cells (CD56+), represented as percentages of total human CD45-positive cells harvested from bone marrows, spleens, and PB from humanized NSG mice 32 weeks postintrahepatic injection into pups. (c) Distribution of CAR-positive cells by different human hematopoietic lineages in humanized mice, NK cells (CD56+), myeloid cells (CD33+), B-lymphocytes (CD19+), and T-lymphocytes (CD3+), represented as percentages of total human CD45-positive cells harvested from bone marrows (BM), spleens (Sp), and PB from humanized NSG mice 32 weeks postintrahepatic injection into pups of nontransduced human HSPCs (NT) or CAR-transduced human HSPCs (CD19R or CD19RCD28). Values represent arithmetic means of results from three experiments and error bars represent mean+SEM. (d) Representative flow cytometry dot plots of BM and PB of a humanized mouse injected with CD19R-modified human HSPCs. Human cell surface markers CD56, CD33, CD19, and CD3 were plotted against CAR expression detected by FITC-conjugated F(ab′)2 fragment goat antihuman IgG1 Fcγ. NSG, NOD/SCID/γ chainnull; PB, peripheral blood.