Full restoration of human platelets in humanized mice after mouse macrophage depletion. (A) Human platelets (1.5 × 10⁷) were intravenously injected into macrophage-depleted (CLD; n = 3) or control (PBS; n = 3) NSG mice. Blood was collected at the indicated time points and the percentages of injected human platelets were analyzed by flow cytometry. Shown are representative flow cytometric profiles (left) and kinetic levels (mean ± SEM; right) of huCD42a⁺ human platelets at the indicated time points after platelet transfusion. Macrophage depletion was performed by intravenous injection of clodronate-liposomes (CLD) at day 3 (100 μL) and day 1 (50 μL) with respect to human platelet injection (day 0); control mice were treated with PBS-liposomes at same volumes and schedule. (B) Blood was collected from 12-week humanized NOD/SCID mice (n = 5) before (Before) and 1 week after (1 week) injection of clodronate-liposomes, and the levels of human CD42a⁺ platelet and human CD45⁺ PBMC chimerism were determined by flow cytometry. Shown are ratios (mean ± SEM) of human CD42a⁺ platelet chimerism to CD45⁺ PBMC chimerism (left) and flow cytometry profiles showing human platelet chimerism (right) before and 1 week after treatment with CLD. (C) Thirteen-week humanized NOD/SCID mice were treated with CLD (n = 4) or PBS-liposomes (n = 3; 100 μL at days 0, 2, 7, 12, 17, and 22). Blood was collected 1 week before and at several time points after treatment, and the levels of human platelets and human PBMCs were determined by flow cytometry. Shown are levels (mean ± SEMs) of human platelet chimerism at the indicated times (left), representative flow cytometry profiles at week 3 after treatment (middle), and percentages (mean ± SEM) of human platelet versus CD45⁺ PBMC chimerism at week 3 after treatment (right). NS indicates not significant.