Abstract
Hematopoietic cells of various lineages are organized in distinct cellular architectures in the bone marrow hematopoietic compartment (BMHC). The homogeneous Kroghian model, which deals only with a single cell type, may not be sufficient to accurately describe oxygen transfer in the BMHC. Thus, for cellular architectures of physiological significance, more complex biophysical-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 the multilayer Kroghian model. We have also developed two-dimensional Kroghian models to simulate several cellular architectures in which a cell cluster (erythroid cluster) or an individual cell (megakaryocyte or adipocyte) is located in the BMHC predominantly occupied by mature granulocytes. pO(2) distributions in colony-type cellular arrangements (erythroblastic islets, granulopoietic loci, and lymphocytic nodules) in the BMHC were also evaluated by modifying the multilayer Kroghian model. The simulated results indicate that most hematopoietic progenitors experience low pO(2) values, which agrees with the finding that low pO(2) promotes the expansion of various hematopoietic progenitors. These results suggest that the most primitive stem cells, which are located even further away from BM sinuses, are likely located in a very low pO(2) environment.
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- CALIGARA F., ROOTH G. Measurement of the oxygen diffusion coefficient in the subcutis of man. Acta Physiol Scand. 1961 Oct;53:114–127. doi: 10.1111/j.1748-1716.1961.tb02269.x. [DOI] [PubMed] [Google Scholar]
- Chow D. C., Wenning L. A., Miller W. M., Papoutsakis E. T. Modeling pO(2) distributions in the bone marrow hematopoietic compartment. I. Krogh's model. Biophys J. 2001 Aug;81(2):675–684. doi: 10.1016/S0006-3495(01)75732-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collins P. C., Nielsen L. K., Patel S. D., Papoutsakis E. T., Miller W. M. Characterization of hematopoietic cell expansion, oxygen uptake, and glycolysis in a controlled, stirred-tank bioreactor system. Biotechnol Prog. 1998 May-Jun;14(3):466–472. doi: 10.1021/bp980032e. [DOI] [PubMed] [Google Scholar]
- Federspiel W. J. A model study of intracellular oxygen gradients in a myoglobin-containing skeletal muscle fiber. Biophys J. 1986 Apr;49(4):857–868. doi: 10.1016/S0006-3495(86)83715-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Federspiel W. J., Popel A. S. A theoretical analysis of the effect of the particulate nature of blood on oxygen release in capillaries. Microvasc Res. 1986 Sep;32(2):164–189. doi: 10.1016/0026-2862(86)90052-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fletcher J. E. On facilitated oxygen diffusion in muscle tissues. Biophys J. 1980 Mar;29(3):437–458. doi: 10.1016/S0006-3495(80)85145-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hevehan D. L., Papoutsakis E. T., Miller W. M. Physiologically significant effects of pH and oxygen tension on granulopoiesis. Exp Hematol. 2000 Mar;28(3):267–275. doi: 10.1016/s0301-472x(99)00150-2. [DOI] [PubMed] [Google Scholar]
- Hoofd L., Bos C., Turek Z. Modelling erythrocytes as point-like O2 sources in a Kroghian cylinder model. Adv Exp Med Biol. 1994;345:893–900. doi: 10.1007/978-1-4615-2468-7_117. [DOI] [PubMed] [Google Scholar]
- Hoofd L., Kreuzer F. A new mathematical approach for solving carrier-facilitated steady-state diffusion problems. J Math Biol. 1979 Jul 13;8(1):1–13. doi: 10.1007/BF00280581. [DOI] [PubMed] [Google Scholar]
- Hoofd L., Turek Z., Rakusan K. Diffusion pathways in oxygen supply of cardiac muscle. Adv Exp Med Biol. 1987;215:171–177. doi: 10.1007/978-1-4684-7433-6_20. [DOI] [PubMed] [Google Scholar]
- Ivanov K. P., Kislayokov Y. Y., Samoilov M. O. Microcirculation and transport of oxygen to neurons of the brain. Microvasc Res. 1979 Nov;18(3):434–441. doi: 10.1016/0026-2862(79)90049-9. [DOI] [PubMed] [Google Scholar]
- Koller M. R., Bender J. G., Miller W. M., Papoutsakis E. T. Reduced oxygen tension increases hematopoiesis in long-term culture of human stem and progenitor cells from cord blood and bone marrow. Exp Hematol. 1992 Feb;20(2):264–270. [PubMed] [Google Scholar]
- LaIuppa J. A., Papoutsakis E. T., Miller W. M. Oxygen tension alters the effects of cytokines on the megakaryocyte, erythrocyte, and granulocyte lineages. Exp Hematol. 1998 Aug;26(9):835–843. [PubMed] [Google Scholar]
- Lichtman M. A. The relationship of stromal cells to hemopoietic cells in marrow. Kroc Found Ser. 1984;18:3–29. [PubMed] [Google Scholar]
- Metzger H. Geometric considerations in modeling transport processes in tissue. Adv Exp Med Biol. 1973;37:761–772. doi: 10.1007/978-1-4684-5089-7_14. [DOI] [PubMed] [Google Scholar]
- Popel A. S. Oxygen diffusive shunts under conditions of heterogeneous oxygen delivery. J Theor Biol. 1982 Jun 21;96(4):533–541. doi: 10.1016/0022-5193(82)90229-6. [DOI] [PubMed] [Google Scholar]
- Rakusan K., Hoofd L., Turek Z. The effect of cell size and capillary spacing on myocardial oxygen supply. Adv Exp Med Biol. 1984;180:463–475. doi: 10.1007/978-1-4684-4895-5_44. [DOI] [PubMed] [Google Scholar]
- Rich I. N. A role for the macrophage in normal hemopoiesis. II. Effect of varying physiological oxygen tensions on the release of hemopoietic growth factors from bone-marrow-derived macrophages in vitro. Exp Hematol. 1986 Sep;14(8):746–751. [PubMed] [Google Scholar]
- Rich I. N., Kubanek B. The effect of reduced oxygen tension on colony formation of erythropoietic cells in vitro. Br J Haematol. 1982 Dec;52(4):579–588. doi: 10.1111/j.1365-2141.1982.tb03934.x. [DOI] [PubMed] [Google Scholar]
- Rich I. N. The macrophage as a production site for hematopoietic regulator molecules: sensing and responding to normal and pathophysiological signals. Anticancer Res. 1988 Sep-Oct;8(5A):1015–1040. [PubMed] [Google Scholar]
- Smith S., Broxmeyer H. E. The influence of oxygen tension on the long-term growth in vitro of haematopoietic progenitor cells from human cord blood. Br J Haematol. 1986 May;63(1):29–34. doi: 10.1111/j.1365-2141.1986.tb07491.x. [DOI] [PubMed] [Google Scholar]