Regression of MECA-32–positive vessels in BM after 5-FU. (A) Regression and regeneration of marrow's vasculature after myelosuppression. In order to quantitate the degree of vascular regression after myelosuppression with 5-FU, the number of sinusoidal vessels was determined using the panendothelial marker MECA-32. At day 7 after myelosuppression, there is a profound regression and disruption of the BM vasculature with dilated and leaky vessels, displaying local disintegration (red arrows). Remarkably, by day 14 there is a gradual regeneration of large nascent vessels (red arrows at days 14 and 24). By day 24 after 5-FU myelosuppression, the large dilated nascent neovessels remodel into small functional fully RBC-loaded vessels decorated by hematopoietic cells, including megakaryocytes (yellow arrows). (B) Quantification of BM vasculature by determination of MECA-32–positive neovessel surface area. MECA-32/hematoxylin-stained BM sections were obtained at different time points after injection of 5-FU. The MECA-32–positive BM surface area was measured by quantification of the brown chroma pixels compared with the total number of pixels in the digital image as described in “Materials and methods.” At steady-state conditions, the surface area of MECA-32–positive cells as normalized to the percentage of total BM hematopoietic cell-surface area is about 7%. Myelosuppression diminishes the surface area index of MECA-32 positive to 2%, reminiscent of the vasculotoxic effects of 5-FU. All results are shown as mean ± standard deviation (n = 4, P < .01 at day 7).