Spatial distribution of blood vessels and CD34+ hematopoietic stem and progenitor cells within the marrow cavities of human cancellous bone

Current bone marrow closimetry methods inherently assume that the target cells of interest for the assessment of leukemia risk (stochastic effects) or marrow toxicity (deterministic effects) are uniformly localized throughout the marrow cavities of cancellous bone. Previous studies on mouse femur, however, have demonstrated a spatial gradient for the hernatopoietic stem and progenitor cells, with higher concentrations near the bone surfaces. The objective of the present study was to directly measure the spatial concentration of these cells, as well as marrow vasculature structures, within images of human disease-free bone marrow. Methods: Core-biopsy samples of normal bone marrow from the iliac crest were obtained from clinical cases at Shands Hospital at the University of Florida Department of Pathology. The specimens were sectioned and immunohistochemically stained for CD34 (red) and CD31 (brown) antigens. These 2 stains were used simultaneously to differentiate between hernatopoietic stem and progenitor cells (CD34(+)/CD31(-)) and vascular endothelium (CD34(+)/CD311(+)). Distances from hematopoietic CD34(+) cells and blood vessels to the nearest bone trabecula surface were measured digitally and then binned in 50-mu m increments, with the results then normalized per unit area of marrow tissue. The distances separating hematopoietic CD34(+) cells from vessels were also tallied. Results: Hematopoietic CD34(+) cells were found to exist along a linear spatial gradient with a maximal areal concentration localized within the first 50 mu m of the bone surfaces. An exponential spatial concentration gradient was found in the concentration of blood vessel fragments within the images. Distances between hernatopoietic CD34(+) cells and blood vessels exhibited a lognormal distribution indicating a shared spatial niche. Conclusion: Study results confirm that the spatial gradient of hematopoietic stem and progenitor cells previously measured in mouse femur is also present within human cancellous bone. The closimetric implication of these results may be significant for those scenarios in which the absorbed dose itself is nonuniformly delivered across the marrow tissues, as would be the case for a low-energy P- or a-particle emitter localized on the bone surfaces.