Stiehl Thomas, Ho Anthony D, Marciniak-Czochra Anna
Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Heidelberg, Germany.
Adv Exp Med Biol. 2014;844:347-67. doi: 10.1007/978-1-4939-2095-2_17.
Hematopoiesis is a complex and strongly regulated process. In case of regenerative pressure, efficient recovery of blood cell counts is crucial for survival of an individual. We propose a quantitative mathematical model of white blood cell formation based on the following cell parameters: (1) proliferation rate, (2) self-renewal, and (3) cell death. Simulating this model we assess the change of these parameters under regenerative pressure. The proposed model allows to quantitatively describe the impact of these cell parameters on engraftment time after stem cell transplantation. Results indicate that enhanced self-renewal during the posttransplant period is crucial for efficient regeneration of blood cell counts while constant or reduced self-renewal leads to delayed recovery or graft failure. Increased cell death in the posttransplant period has a similar impact. In contrast, reduced proliferation or pre-homing cell death causes only mild delays in blood cell recovery which can be compensated sufficiently by increasing the dose of transplanted cells.
造血是一个复杂且受到严格调控的过程。在再生压力的情况下，血细胞计数的有效恢复对于个体的生存至关重要。我们基于以下细胞参数提出了一个白细胞生成的定量数学模型：（1）增殖率，（2）自我更新，以及（3）细胞死亡。通过模拟这个模型，我们评估了再生压力下这些参数的变化。所提出的模型能够定量描述这些细胞参数对干细胞移植后植入时间的影响。结果表明，移植后期间自我更新的增强对于血细胞计数的有效再生至关重要，而自我更新保持恒定或降低则会导致恢复延迟或移植失败。移植后期间细胞死亡增加也有类似影响。相比之下，增殖减少或归巢前细胞死亡仅会导致血细胞恢复出现轻微延迟，通过增加移植细胞剂量可充分补偿这种延迟。
