, Volume 41, Issue 5, pp 335–346 | Cite as

Computer model of hemopoietic stem cell population testing a possible role of DNA synthesizing cells in proliferation control

  • E. Nečas
  • F. Hauser
  • J. Neuwirt
Original Works


A computer model of the stem cell population is presented. Proliferation control is achieved solely in this model by a feedback, which changes the flow of cells from the g0 state into the g1 phase according to the amount of the DNA synthesizing S phase cells. Behavior of the model was compared with experimental data available about the CFUs (colony-forming units — spleen) cell population. A reasonable agreement between simulation results and experimental data could be obtained provided that some cells do not pass through the G0 state during their cell cycle. Necessity to establish the seeding efficiency of the spleen colony technique arose when experimental CFUs data showing pluripotential stem cells response to hydroxyurea damage were compared with results obtained from the model.

Key words

Proliferation control S phase Computer model Hydroxyurea Seeding efficiency 


Es wird ein Computer-Modell für die Stammzellpopulation vorgestellt. Die Proliferationskontrolle wird in diesem Modell nur durch eine Rückkopplung erreicht, die den Zellfluß von der G0- in die G1-Phase aufgrund der Anzahl der S-Phase-Zellen, die DNA synthetisieren, ändert. Das Verhalten des Modells wurde mit experimentellen Daten verglichen, die aus der Analyse der CFUs-Zellpopulation stammen. Es besteht eine brauchbare Übereinstimmung zwischen den errechneten und experimentellen Daten, vorausgesetzt, daß einzelne Zellen während ihres Zellzyklus die G0-Phase nicht passieren. Wenn die experimentellen CFUs-Daten von pluripotenten Stammzellen nach einer Hydroxyharnstoff-Schädigung mit den Ergebnissen des Modells verglichen werden, besteht die Notwendigkeit, die Angehrate der Milzkolonietechnik zu bestimmen.


Proliferationskontrolle S-Phase Computer-Modell Hydroxy-harnstoff Angehrate 


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  1. 1.
    Becker AJ, McCulloch EA, Siminovitch I., Till JE (1965) The effect of differing demands for blood cell production on DNA synthesis by hemopoietic colony-forming cells of mice. Blood 26: 296–308 1965Google Scholar
  2. 2.
    Blackett NM (1976) Cell cycle characteristics of hemopoietic stem cells. In: Cairnie AB, Lala PK, Osmond DG (eds) Stem cells of renewing cell populations. Academic Press, New York-San Francisco-London, pp 157–164Google Scholar
  3. 3.
    Brown JM (1968) Long G1 or G0 state: a method of resolving the dilemma for the cell cycle of an in vivo population. Exp Cell Res 52: 565–570Google Scholar
  4. 4.
    De Maertelaer V, Galand P (1975) Some properties of a ◂G0” model of the cell cycle. I. Investigation on the possible existence of natural constraints on the theoretical model in steady-state conditions. Cell Tissue Kinet 8: 11–22Google Scholar
  5. 5.
    Hauser F, Necas E (1977) A model of proliferation control in the population of hemopoietic stem cells. In: IFAC-Symposium on Control Mechanisms in Bio- and Ecosystems, vol. 4, 1977, pp 174–182, LeipzigGoogle Scholar
  6. 6.
    Hauser F, Nečas E (1980) A model of proliferation control in the population of hemopoietic stem cells. Acta Univ Carol Med (in press)Google Scholar
  7. 7.
    Hauser F, Kotva M, Necas E, Neuwirt J, Pokorný Z (1976) Model of stem cell population of blood forming tissues. In: Dekker I.(ed) Simulation of systems. North-Holland Publishing Company, Amsterdam, pp 591–597Google Scholar
  8. 8.
    Hodgson GS, Bradley TR, Martin RF, Sumner M, Fry P (1975) Recovery of proliferating hemopoietic progenitor cells after killing by hydroxyurea. Cell Tissue Kinet 8: 51–60Google Scholar
  9. 9.
    Kirk J, Orr J, Hope CS (1968) A mathematical analysis of red blood cell and bone marrow stem cell mechanism. Br J Haematol 15: 35–46Google Scholar
  10. 10.
    Lajtha LG, Oliver R Gurney CW(1962) Kinetic model of a bone marrow stem cell population. Br J Haematol 8: 442–460Google Scholar
  11. 11.
    Lajtha LG, Pozzi LV, Schofield R, Fox M (1969) Kinetic properties of hemopoietic stem cells. Cell Tissue Kinet 2: 39–49Google Scholar
  12. 12.
    Lord BI (1970) Measurement of the duration of DNA synthesis in erythroid cells of the bone marrow using a double labelling autoradiographic technique designed specifically for use with hemopoietic tissue. Cell Tissue Kinet 3: 13–19Google Scholar
  13. 13.
    Morse BS, Rencricca NJ, Stohlman F Jr (1970) Relationship of erythropoietin effectiveness to the generative cycle of erythroid precursor cell. Blood 35: 761–774Google Scholar
  14. 14.
    Necas E, Neuwirt J (1976a) Control of hemopoietic stem cell proliferation by cells in DNA synthesis. Br J Haematol 33: 233–230Google Scholar
  15. 15.
    Necas E, Neuwirt J (1976b) Proliferation rate of hemopoietic stem cells after damage by several cytostatic agents. Cell Tissue Kinet 9: 479–487Google Scholar
  16. 16.
    Necas E, Neuwirt J (1977) Effect of hydroxyurea and vinblastine on the proliferation of the pluripotential stem cells. Neoplasma 24: 29–40Google Scholar
  17. 17.
    Nečas E, Ponka P, Neuwirt J (1978) Changes in stem cell compartments in mice after hydroxyurea. Cell Tissue Kinet 11: 119–127Google Scholar
  18. 18.
    Necas E, Ponka P, Neuwirt J (1979) Estimation of the pluripotential stem cells in bone marrow after hydroxyurea. In: Heimpel H, Gordon-Smith EC, Heit W, Kubanek B (eds) Aplastic anemia. Pathophysiology and approaches to therapy. Springer, Berlin Heidelberg New York, pp 83–86Google Scholar
  19. 19.
    Porteous DD, Lajtha LG (1966) On stem cell recovery after irradiation. Br J Haematol 12: 177–188Google Scholar
  20. 20.
    Rajewsky MD, Hulser DF, Febricius E (1971) Untersuchungen zur Synchronisation in vivo: Temporäre Inhibition der DNA-Synthese durch Hydroxyharnstoff in normalen und malignen Säugerzellsystemen. Z Krebsforsch 76: 266–292Google Scholar
  21. 21.
    Morse BS, Rencricca NJ, Stohlman F Jr (1969) The effect of hydroxyurea on differentiated marrow erythroid precursors. Proc Soc Exp Biol Med 130: 986–989Google Scholar
  22. 22.
    Steel GG (1972) The cell cycle in tumours: an examination of data gained by the technique of labelled mitosis. Cell Tissue Kinet 5: 87–100Google Scholar
  23. 23.
    Tarbutt RG, Blackett NM (1968) Cell population kinetics of the recognizable erythroid cells in the rat. Cell Tissue Kinet 1: 65–84Google Scholar
  24. 24.
    Till JE, McCulloch EA (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 14: 213–222Google Scholar
  25. 25.
    Vassort F, Winterholer M, Frindel E, Tubiana M (1973) Kinetic parameters of bone marrow stem cells using in vivo suicide by tritiated thymidine or by hydroxyurea. Blood 41: 789–796Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • E. Nečas
    • 1
  • F. Hauser
    • 2
  • J. Neuwirt
    • 1
  1. 1.Department of Pathological Physiology, Faculty of General MedicineCharles UniversityPrague 2Czechoslovakia
  2. 2.Hybrid Computation LaboratoryInstitute for Social Medicine and Organization of Health ServicesPragueCzechoslovakia

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