Bone marrow regeneration under cytotoxic drug regimens: behaviour ranging from homeostasis to unpredictability in a model for hemopoietic differentiation.

In the process of hemopoiesis, bone marrow stem cells differentiate into the various types of mature blood cells. We present a model for bone marrow dynamics, which retrieves its ability to continuously modulate the balance between self-renewal and differentiation, even under periodic cytodestructive perturbations. Yet, a temporally stochastic perturbation results in chaotic-like behaviour which has no deterministic source.

[1]  W. Freeman,et al.  How brains make chaos in order to make sense of the world , 1987, Behavioral and Brain Sciences.

[2]  S. Watt,et al.  An improved negative immunomagnetic selection strategy for the purification of primitive hemopoietic cells from normal bone marrow. , 1991, Experimental hematology.

[3]  I. Bertoncello,et al.  The resolution, enrichment, and organization of normal bone marrow high proliferative potential colony-forming cell subsets on the basis of rhodamine-123 fluorescence. , 1991, Experimental hematology.

[4]  J. Visser,et al.  Purification of pluripotent hemopoietic stem cells: past and present. , 1990, Experimental hematology.

[5]  I. Weissman,et al.  Purification and characterization of mouse hematopoietic stem cells. , 1988, Science.

[6]  A. Dawson.  Bailliere's Clinical Haematology - International Practice and Research , 1988 .

[7]  Gade,et al.  Characterizing loss of memory in a dynamical system. , 1990, Physical review letters.

[8]  I. Bernstein,et al.  Recombinant human stem cell factor enhances the formation of colonies by CD34+ and CD34+lin- cells, and the generation of colony-forming cell progeny from CD34+lin- cells cultured with interleukin-3, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor. , 1991, Blood.

[9]  Zvia Agur,et al.  Reduction of cytotoxicity to normal tissues by new regimens of cell-cycle phase-specific drugs , 1988 .

[10]  S. Newhouse,et al.  The abundance of wild hyperbolic sets and non-smooth stable sets for diffeomorphisms , 1979 .

[11]  M. Loeffler,et al.  A concept of hemopoietic regulation and its biomathematical realization. , 1988, Blood cells.

[12]  D. Metcalf,et al.  The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells , 1989, Nature.

[13]  K. Atkinson,et al.  Reconstruction of the haemopoietic and immune systems after marrow transplantation. , 1990, Bone marrow transplantation.

[14]  V. Diehl,et al.  Differential effects of recombinant human colony stimulating factor (rh G‐CSF) on stem cells in marrow, spleen and peripheral blood in mice , 1990, British journal of haematology.

[15]  R. Pool.  Is it healthy to be chaotic? , 1989, Science.

[16]  S. Renals,et al.  A study of network dynamics , 1990 .

[17]  P. Grassberger,et al.  Characterization of Strange Attractors , 1983 .

[18]  D. Williams,et al.  Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells. , 1991, Blood.

[19]  P. Quesenberry,et al.  Multifactor stimulation of megakaryocytopoiesis: effects of interleukin 6. , 1991, Experimental hematology.

[20]  Sommers,et al.  Chaos in random neural networks. , 1988, Physical review letters.

[21]  Zvia Agur,et al.  Randomness, synchrony and population persistence , 1985 .

[22]  P. Waring,et al.  Gliotoxin treatment selectively spares M‐CSF‐ plus IL‐3‐responsive multipotent haemopoietic progenitor cells in bone marrow , 1991, European journal of haematology.

[23]  E. Wright,et al.  Identification and characterization of an inhibitor of haemopoietic stem cell proliferation , 1990, Nature.

[24]  P. Furmanski,et al.  Negative regulators of in vivo erythropoiesis: interaction of IL-1 alpha and TNF-alpha and the lack of a strict requirement for T or NK cells for their activity. , 1991, Experimental hematology.

[25]  H. Nakauchi,et al.  Effects of interleukin 3, interleukin 6, and granulocyte colony-stimulating factor on sorted murine splenic progenitor cells. , 1991, Experimental hematology.

[26]  L. Šefc,et al.  Haemopoietic stem cells: spleen colony‐forming cells are normally actively proliferating , 1990, Cell and tissue kinetics.

[27]  A. Babloyantz,et al.  Low-dimensional chaos in an instance of epilepsy. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[28]  K. Zsebo,et al.  The role of recombinant stem cell factor in early B cell development. Synergistic interaction with IL-7. , 1991, Journal of immunology.

[29]  D. Zipori.  Regulation of hemopoiesis by cytokines that restrict options for growth and differentiation. , 1990, Cancer cells.

[30]  S. Newhouse,et al.  Diffeomorphisms with infinitely many sinks , 1974 .

[31]  P. Grassberger,et al.  Measuring the Strangeness of Strange Attractors , 1983 .

[32]  C. Eaves,et al.  Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[33]  R. Schofield.  The relationship between the spleen colony-forming cell and the haemopoietic stem cell. , 1978, Blood cells.

[34]  D. Ruelle,et al.  Ergodic theory of chaos and strange attractors , 1985 .

[35]  J. Deneubourg,et al.  The effect of environmental disturbances on the dynamics of marine intertidal populations , 1985 .

[36]  R. May,et al.  Stability and Complexity in Model Ecosystems , 1976, IEEE Transactions on Systems, Man, and Cybernetics.

[37]  E. Nečas,et al.  Non‐Circadian Rhythm In Proliferation of Haematopoietic Stem Cells , 1988, Cell and tissue kinetics.