Mathematical Models of Hematopoietic Reconstitution After Stem Cell Transplantation
Transplantation of bone marrow stem cells is a widely used option to treat leukemias and other diseases. Nevertheless this intervention is linked to life-threatening complications. Numerous clinical trials have been performed to evaluate various treatment
- PDF / 729,940 Bytes
- 16 Pages / 439.36 x 666.15 pts Page_size
- 83 Downloads / 245 Views
Abstract Transplantation of bone marrow stem cells is a widely used option to treat leukemias and other diseases. Nevertheless this intervention is linked to lifethreatening complications. Numerous clinical trials have been performed to evaluate various treatment options. Since there exist strong interindividual variations in patients’ responses, results of clinical trials are hardly applicable to individual patients. In this paper a mathematical model of hematopoiesis introduced by us in (Marciniak-Czochra et al.: Stem Cells Dev. 18:377–85, 2009) is calibrated based on clinical data and applied to study several aspects of short term reconstitution after bone marrow transplantation. Parameter estimation is performed based on the data of time evolution of leukocyte counts after chemotherapy and bone marrow transplantation obtained for individual patients. The model allows to simulate various treatment options for large groups of individual patients, to compare the effects of the treatments on individual patients and to evaluate how the properties of the transplant and cytokine treatment affect the time of reconstitution. Keywords Differential equations • Hematopoiesis • Mathematical model • Stem cell transplantation
1 Introduction Stem cell research is an important field of life sciences with promising clinical impacts. During last years an enormous amount of information on specific factors, genes and cellular interactions involved in tissue homeostasis, cell differentiation
A. Marciniak-Czochra () T. Stiehl Interdisciplinary Center for Scientific Computing, Im Neuenheimer Feld 368, 69120 Heidelberg, Germany e-mail: [email protected]; [email protected] H.G. Bock et al. (eds.), Model Based Parameter Estimation, Contributions in Mathematical and Computational Sciences 4, DOI 10.1007/978-3-642-30367-8 9, © Springer-Verlag Berlin Heidelberg 2013
191
192
A. Marciniak-Czochra and T. Stiehl
and stem cell function has been collected. However, the precise mechanisms regulating stem cell self-renewal, maintenance and differentiation in clinically important scenarios are still poorly understood. Mathematical modelling has evolved as an important tool in describing and understanding of bio-medical processes. Such processes are characterised by a high level of complexity. In most cases important sub-processes are poorly defined or not known. This fact and the mathematical or computational complexity of resulting models make it impossible and useless to include all involved processes into a mathematical model. Nevertheless mathematical modelling is a powerful tool in addressing specific biological questions or in comparing different well defined hypotheses. In higher organisms, a steady supply of somatic cells is accomplished by proliferation of corresponding stem cells, which retain the capability for almost indefinite self-renewal. Driven by hormonal signals from the organism, some stem cells commit to differentiation and maturation into specialised lineages. Organs and tissues of
Data Loading...
