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

Abstract

Human bone marrow (BM) is a tissue of complex architectural organization, which includes granulopoietic loci, erythroblastic islets, and lymphocytic nodules. Oxygen tension (pO(2)) is an important determinant of hematopoietic stem and progenitor cell proliferation and differentiation. Thus, understanding the impact of the BM architectural organization on pO(2) levels in extravascular hematopoietic tissue is an important biophysical problem. However, currently it is impossible to measure pO(2) levels and their spatial variations in the BM. Homogeneous Kroghian models were used to estimate pO(2) distribution in the BM hematopoietic compartment (BMHC) and to conservatively simulate pO(2)-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 pO(2) 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 pO(2) depletion in the extravascular tissue. Modeling results suggest that stem and progenitor cells experience a low pO(2) environment in the BMHC.

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Selected References

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  1. BIRD R. M., CLEMENTS J. A., BECKER L. M. The metabolism of leukocytes taken from peripheral blood of leukemic patients. Cancer. 1951 Sep;4(5):1009–1014. doi: 10.1002/1097-0142(195109)4:5<1009::aid-cncr2820040516>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  2. Bathija A., Davis S., Trubowitz S. Bone marrow adipose tissue: response to acute starvation. Am J Hematol. 1979;6(3):191–198. doi: 10.1002/ajh.2830060303. [DOI] [PubMed] [Google Scholar]
  3. Bradley T. R., Hodgson G. S., Rosendaal M. The effect of oxygen tension on haemopoietic and fibroblast cell proliferation in vitro. J Cell Physiol. 1978 Dec;97(3 Pt 2 Suppl 1):517–522. doi: 10.1002/jcp.1040970327. [DOI] [PubMed] [Google Scholar]
  4. Brizel D. M., Dodge R. K., Clough R. W., Dewhirst M. W. Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol. 1999 Nov;53(2):113–117. doi: 10.1016/s0167-8140(99)00102-4. [DOI] [PubMed] [Google Scholar]
  5. Böttcher H., Engel S., Fürst P. Determination of gaseous and dissolved oxygen in a closed fat cell culture system. Anal Biochem. 1995 Sep 1;230(1):149–153. doi: 10.1006/abio.1995.1449. [DOI] [PubMed] [Google Scholar]
  6. Carmeliet P., Jain R. K. Angiogenesis in cancer and other diseases. Nature. 2000 Sep 14;407(6801):249–257. doi: 10.1038/35025220. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Dutta A., Popel A. S. A theoretical analysis of intracellular oxygen diffusion. J Theor Biol. 1995 Oct 21;176(4):433–445. doi: 10.1006/jtbi.1995.0211. [DOI] [PubMed] [Google Scholar]
  9. Gnaiger E., Steinlechner-Maran R., Méndez G., Eberl T., Margreiter R. Control of mitochondrial and cellular respiration by oxygen. J Bioenerg Biomembr. 1995 Dec;27(6):583–596. doi: 10.1007/BF02111656. [DOI] [PubMed] [Google Scholar]
  10. Gottfried E. L. Lipids of human leukocytes: relation to celltype. J Lipid Res. 1967 Jul;8(4):321–327. [PubMed] [Google Scholar]
  11. Grunewald W. A., Sowa W. Distribution of the myocardial tissue PO2 in the rat and the inhomogeneity of the coronary bed. Pflugers Arch. 1978 Apr 25;374(1):57–66. doi: 10.1007/BF00585697. [DOI] [PubMed] [Google Scholar]
  12. Hansen-Algenstaedt N., Stoll B. R., Padera T. P., Dolmans D. E., Hicklin D. J., Fukumura D., Jain R. K. Tumor oxygenation in hormone-dependent tumors during vascular endothelial growth factor receptor-2 blockade, hormone ablation, and chemotherapy. Cancer Res. 2000 Aug 15;60(16):4556–4560. [PubMed] [Google Scholar]
  13. Hedeskov C. J., Esmann V. Respiration and glycolysis of normal human lymphocytes. Blood. 1966 Aug;28(2):163–174. [PubMed] [Google Scholar]
  14. Helmlinger G., Yuan F., Dellian M., Jain R. K. Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med. 1997 Feb;3(2):177–182. doi: 10.1038/nm0297-177. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Ishikawa Y., Ito T. Kinetics of hemopoietic stem cells in a hypoxic culture. Eur J Haematol. 1988 Feb;40(2):126–129. doi: 10.1111/j.1600-0609.1988.tb00808.x. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Katahira J., Mizoguchi H. Improvement of culture conditions for human megakaryocytic and pluripotent progenitor cells by low oxygen tension. Int J Cell Cloning. 1987 Sep;5(5):412–420. doi: 10.1002/stem.5530050506. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Krogh A. The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary for supplying the tissue. J Physiol. 1919 May 20;52(6):409–415. doi: 10.1113/jphysiol.1919.sp001839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Krogh A. The rate of diffusion of gases through animal tissues, with some remarks on the coefficient of invasion. J Physiol. 1919 May 20;52(6):391–408. doi: 10.1113/jphysiol.1919.sp001838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Leunig M., Yuan F., Menger M. D., Boucher Y., Goetz A. E., Messmer K., Jain R. K. Angiogenesis, microvascular architecture, microhemodynamics, and interstitial fluid pressure during early growth of human adenocarcinoma LS174T in SCID mice. Cancer Res. 1992 Dec 1;52(23):6553–6560. [PubMed] [Google Scholar]
  25. Lichtman M. A. The relationship of stromal cells to hemopoietic cells in marrow. Kroc Found Ser. 1984;18:3–29. [PubMed] [Google Scholar]
  26. Lichtman M. A. The ultrastructure of the hemopoietic environment of the marrow: a review. Exp Hematol. 1981 Apr;9(4):391–410. [PubMed] [Google Scholar]
  27. Marcus A. J., Ullman H. L., Safier L. B. Lipid composition of subcellular particles of human blood platelets. J Lipid Res. 1969 Jan;10(1):108–114. [PubMed] [Google Scholar]
  28. Mostafa S. S., Miller W. M., Papoutsakis E. T. Oxygen tension influences the differentiation, maturation and apoptosis of human megakaryocytes. Br J Haematol. 2000 Dec;111(3):879–889. [PubMed] [Google Scholar]
  29. Peng C. A., Palsson B. O. Determination of specific oxygen uptake rates in human hematopoietic cultures and implications for bioreactor design. Ann Biomed Eng. 1996 May-Jun;24(3):373–381. doi: 10.1007/BF02660886. [DOI] [PubMed] [Google Scholar]
  30. Popel A. S. Theory of oxygen transport to tissue. Crit Rev Biomed Eng. 1989;17(3):257–321. [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Roh H. D., Boucher Y., Kalnicki S., Buchsbaum R., Bloomer W. D., Jain R. K. Interstitial hypertension in carcinoma of uterine cervix in patients: possible correlation with tumor oxygenation and radiation response. Cancer Res. 1991 Dec 15;51(24):6695–6698. [PubMed] [Google Scholar]
  33. Stroeve P. Diffusion with irreversible chemical reaction in heterogeneous media: application to oxygen transport in respiring tissue. J Theor Biol. 1977 Jan 21;64(2):237–251. doi: 10.1016/0022-5193(77)90354-x. [DOI] [PubMed] [Google Scholar]
  34. Tavassoli M. Differential response of bone marrow and extramedullary adipose cells to starvation. Experientia. 1974 Apr 15;30(4):424–425. doi: 10.1007/BF01921701. [DOI] [PubMed] [Google Scholar]
  35. Vaupel P., Hoeckel M. Predictive power of the tumor oxygenation status. Adv Exp Med Biol. 1999;471:533–539. doi: 10.1007/978-1-4615-4717-4_63. [DOI] [PubMed] [Google Scholar]
  36. Weiss L. The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anat Rec. 1976 Oct;186(2):161–184. doi: 10.1002/ar.1091860204. [DOI] [PubMed] [Google Scholar]