Effects of NIP-004 on human megakaryopoiesis in xenotransplanted murine bone marrow. (A) NIP-004 increased HuCD41a⁺ megakaryocytes, but not MuCD41⁺ megakaryocytes, in NOG mice receiving xenotransplants. (B) NIP-004 had no significant effect on the number of total nucleated cells and the percentage of other cell lines in murine BM. (C) NIP-004 increased the number of human megakaryocytic progenitor cells (HuCD45⁺CD34⁺CD41a⁺) but not HuCD45⁺CD34⁺ hematopoietic progenitor cells. (D) FACS analysis of DNA ploidy of HuCD41⁺ megakaryocytes. NIP-004 induced maturation of human megakaryocytes in the BM of NOG mice receiving xenotransplants. Data in panels A-D are expressed as mean ± SEM (n = 3). *P < .05, **P < .01 between NIP-004 and vehicle. N.S. indicates no significant difference compared with vehicle. Similar results were obtained from 2 independent experiments. (E-F) Immunohistochemical staining of xenotransplanted murine BM with a monoclonal antibody against human integrin GPIb (HuCD42b). Sections were obtained from the femurs of mice treated with vehicle (E) or NIP-004 (F). Bars, 200 μm.