Modeling pO(2) distributions in the bone marrow hematopoietic compartment.I. Krogh's model

Human bone marrow (BM) is a tissue of complex architectural organization, w hich includes granulopoietic loci, erythroblastic islets, and lymphocytic n odules. Oxygen tension (pO(2)) is an important determinant of hematopoietic stem and progenitor cell proliferation and differentiation. Thus, understa nding the impact of the BM architectural organization on pO(2) levels in ex travascular hematopoietic tissue is an important biophysical problem. Howev er, currently it is impossible to measure pO(2) levels and their spatial va riations in the BM. Homogeneous Kroghian models were used to estimate pO(2) distribution in the BM hematopoietic compartment (BMHC) and to conservativ ely simulate pO(2)-limited cellular architectures. Based on biophysical dat a of hematopoietic cells and characteristics of BM physiology, we construct ed a tissue cylinder solely occupied by granulocytic progenitors (the most metabolically active stage of the most abundant cell type) to provide a phy siologically relevant limiting case. Although the number of possible cellul ar architectures is large, all simulated pO(2) profiles fall between two ex treme cases: those of homogeneous tissues with adipocytes and granulocytic progenitors, respectively. This was illustrated by results obtained from a parametric criterion derived for pO(2) depletion in the extravascular tissu e. Modeling results suggest that stem and progenitor cells experience a low pO(2) environment in the BMHC.