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Kinetic analysis of minimal residual disease using 3-dimentinal computational models of human granulopoiesis and development of risk of relapse-stratified treatment of pediatric leukemia.

使用人类粒细胞生成的三维计算模型对微小残留病进行动力学分析，并制定儿童白血病复发分层治疗的风险。

基本信息

批准号：
17591073
负责人：
SAIKAWA Yutaka
金额：
$ 2.3万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

In 2005, we attempted to develop a unique computational model of human granulopoiesis to identify the regulatory mechanisms for homeostatic hematopoiesis. A computational approach with mathematical-modeling of the hematopoietic system has been applied for exploring the principles that underlie the system. Models are required of easy access and highly expected to integrate details and reproduce the dynamic behaviors of the cells but also to predict the specific cellular behaviors in response to various simulations. We have successfully developed a new lateral computational modeling for human granulopoiesis using three-dimensional Cellular Automata (3D-CA), which incorporates a spatio-temporal concept to describe the granulopoietic process developing in the finite space of bone marrow cavity. We emphasize unique properties of this model as following ; 1)the model does not contain either governing equations or negative feedback loops assumed for regulation and 2)one can directly view this in silico granulopoiesis on the computer screen, in which HSCs replicate, differentiate, and distribute their offspring in an analytical space consisting of 130 x 130 x 130 unit cubic areas with structural objects assuming vessels and trabecular bones. The model reified the principle that local interaction of individual granulopoietic cells produced feedback circuits leading global dynamics and stability of the system.In 2006, we further applied this model to analyze cellular dynamics of granulopoiesis under chemotherapy and hematopoietic stem cell transplantation. Simulation studies predicted efficacy and minimal requirement of G-CSF scheduling for drug-induced neutropenia. Cellular dynamics of homing HSCs explained difference of engraftment periods observed in different utilization of stem cell sources in transplantation. Learning cellular behaviors from computational hematology could provide the novel strategies for the treatment of hematological malignancies.

2005年，我们试图开发一种独特的人类粒细胞生成的计算模型，以确定动态平衡造血的调节机制。一种对造血系统进行数学建模的计算方法已被应用于探索该系统背后的原理。模型不仅要求易于访问，而且需要集成细节和重现细胞的动态行为，而且还需要预测特定的细胞行为以响应各种模拟。我们利用三维元胞自动机(3D-CA)成功地开发了一种新的人类粒细胞生成的横向计算模型(3D-CA)，该模型引入了时空的概念来描述骨髓腔有限空间中的粒细胞生成过程。我们强调该模型的独特性质如下：1)该模型既不包含假设用于调节的控制方程或负反馈回路，也不包含假设用于调节的负反馈回路；2)人们可以直接在计算机屏幕上以电子造粒的形式看到这一点，其中HSC在由130×130×130个单位立方体区域组成的分析空间中复制、分化和分布它们的后代，结构对象假设血管和骨小梁。该模型具体化了单个粒系细胞局部相互作用产生反馈回路导致系统全局动力学和稳定性的原理。2006年，我们进一步应用该模型分析了化疗和造血干细胞移植下的粒系细胞动力学。模拟研究预测了G-CSF治疗药物引起的中性粒细胞减少症的有效性和最低要求。归巢造血干细胞的细胞动力学解释了不同干细胞来源在移植中观察到的植入期的差异。从计算血液学中了解细胞的行为可以为血液系统恶性肿瘤的治疗提供新的策略。