Modeling pO₂ distributions in the bone marrow hematopoietic compartment. I. Krogh's model

Human bone marrow (BM) is a tissue of complex architectural organization, which includes granulopoietic loci, erythroblastic islets, and lymphocytic nodules. Oxygen tension (pO₂) is an important determinant of hematopoietic stem and progenitor cell proliferation and differentiation. Thus, understanding the impact of the BM architectural organization on pO₂ levels in extravascular hematopoietic tissue is an important biophysical problem. However, currently it is impossible to measure pO₂ levels and their spatial variations in the BM. Homogeneous Kroghian models were used to estimate pO₂ distribution in the BM hematopoietic compartment (BMHC) and to conservatively simulate pO₂-limited cellular architectures. Based on biophysical data of hematopoietic cells and characteristics of BM physiology, we constructed a tissue cylinder solely occupied by granulocytic progenitors (the most metabolically active stage of the most abundant cell type) to provide a physiologically relevant limiting case. Although the number of possible cellular architectures is large, all simulated pO₂ profiles fall between two extreme cases: those of homogeneous tissues with adipocytes and granulocytic progenitors, respectively. This was illustrated by results obtained from a parametric criterion derived for pO₂ depletion in the extravascular tissue. Modeling results suggest that stem and progenitor cells experience a low pO₂ environment in the BMHC.