Modeling pO(2) distributions in the bone marrow hematopoietic compartment.II. Modified Kroghian models

Hematopoietic cells of various lineages are organized in distinct cellular architectures in the bone marrow hematopoietic compartment (BMHC). The homo geneous Kroghian model, which deals only with a single cell type, may not b e sufficient to accurately describe oxygen transfer in the BMHC. Thus, for cellular architectures of physiological significance, more complex biophysi cal-transport models were considered and compared against simulations using the homogeneous Kroghian model. The effects of the heterogeneity of model parameters on the oxygen tension (pO(2)) distribution were examined using t he multilayer Kroghian model. We have also developed two-dimensional Kroghi an models to simulate several cellular architectures in which a cell cluste r (erythroid cluster) or an individual cell (megakaryocyte or adipocyte) is located in the BMHC predominantly occupied by mature granulocytes. pO(2) d istributions in colony-type cellular arrangements (erythroblastic islets, g ranulopoietic loci, and lymphocytic nodules) in the BMHC were also evaluate d by modifying the multilayer Kroghian model. The simulated results indicat e that most hematopoietic progenitors experience low pO(2) values, which ag rees with the finding that low pO(2) promotes the expansion of various hema topoietic progenitors. These results suggest that the most primitive stem c ells, which are located even further away from BM sinuses, are likely locat ed in a very low pO(2) environment.