Modeling pO2 distributions in the bone marrow hematopoietic compartment.: I.: Krogh's model
Modeling pO2 distributions in the bone marrow hematopoietic compartment.: I.: Krogh's model
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DOI：
10.1016/s0006-3495(01)75732-3
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发表时间：
2001-08-01
影响因子：
3.4
通讯作者：
Papoutsakis, ET
中科院分区：
文献类型：
--
作者：
Chow, DC;Wenning, LA;Papoutsakis, ET
人骨髓（BM）是一种结构复杂的组织，包括粒细胞生成位点、成红细胞胰岛和淋巴细胞结节。氧分压（pO（2））是造血干细胞和祖细胞增殖和分化的重要决定因素。因此，了解骨髓结构组织对血管外造血组织中pO（2）水平的影响是一个重要的生物物理学问题。然而，目前不可能测量BM中的pO（2）水平及其空间变化。均相Kroghian模型用于估计骨髓造血区室（BMHC）中的pO（2）分布，并保守模拟pO（2）限制的细胞结构。基于造血细胞的生物物理数据和BM生理学特征，我们构建了一个仅由粒细胞祖细胞（最丰富的细胞类型的最代谢活性阶段）占据的组织圆柱体，以提供生理学相关的限制情况。虽然可能的细胞结构的数量很大，所有模拟的pO（2）分布都落在两个极端情况之间：分别具有脂肪细胞和粒细胞祖细胞的同质组织。从血管外组织中pO（2）耗竭的参数标准获得的结果说明了这一点。模拟结果表明，干细胞和祖细胞在BMHC中经历低pO（2）环境。
Human bone marrow (BM) is a tissue of complex architectural organization, which includes granulopoietic loci, erythroblastic islets, and lymphocytic nodules. Oxygen tension (pO(2)) is an important determinant of hematopoietic stem and progenitor cell proliferation and differentiation. Thus, understanding the impact of the BM architectural organization on pO(2) levels in extravascular hematopoietic tissue is an important biophysical problem. However, currently it is impossible to measure pO(2) levels and their spatial variations in the BM. Homogeneous Kroghian models were used to estimate pO(2) distribution in the BM hematopoietic compartment (BMHC) and to conservatively simulate pO(2)-limited cellular architectures. Based on biophysical data of hematopoietic cells and characteristics of BM physiology, we constructed a tissue cylinder solely occupied by granulocytic progenitors (the most metabolically active stage of the most abundant cell type) to provide a physiologically relevant limiting case. Although the number of possible cellular architectures is large, all simulated pO(2) profiles fall between two extreme cases: those of homogeneous tissues with adipocytes and granulocytic progenitors, respectively. This was illustrated by results obtained from a parametric criterion derived for pO(2) depletion in the extravascular tissue. Modeling results suggest that stem and progenitor cells experience a low pO(2) environment in the BMHC.