tailieunhanh - Báo cáo y học: "Modeling the clonal heterogeneity of stem cells"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài:Modeling the clonal heterogeneity of stem cells. | Tuck and Miranker Theoretical Biology and Medical Modelling 2010 7 44 http content 7 1 44 THEORETICAL BIOLOGY AND MEDICAL MODELLING RESEARCH Open Access Modeling the clonal heterogeneity of stem cells David P Tuck1 Willard Miranker2 Correspondence . edu department of Pathology Pathology Informatics Yale University School of Medicine New Haven Connecticut 06510 USA 2 BioMed Central Abstract Recent experimental studies suggest that tissue stem cell pools are composed of functionally diverse clones. Metapopulation models in ecology concentrate on collections of populations and their role in stabilizing coexistence and maintaining selected genetic or epigenetic variation. Such models are characterized by expansion and extinction of spatially distributed populations. We develop a mathematical framework derived from the multispecies metapopulation model of Tilman et al 1994 to study the dynamics of heterogeneous stem cell metapopulations. In addition to normal stem cells the model can be applied to cancer cell populations and their response to treatment. In our model disturbances may lead to expansion or contraction of cells with distinct properties reflecting proliferation apoptosis and clonal competition. We first present closed-form expressions for the basic model which defines clonal dynamics in the presence of exogenous global disturbances. We then extend the model to include disturbances which are periodic and which may affect clones differently. Within the model framework we propose a method to devise an optimal strategy of treatments to regulate expansion contraction or mutual maintenance of cells with specific properties. Background The promise of therapeutic applications of stem cells depends on expansion purification and differentiation of cells of specific types required for different clinical purposes. Stem cells are defined by the capacity to either self-renew or differentiate into multiple cell lineages. These characteristics