Compressed vessels bias red blood cell partitioning at bifurcations in a hematocrit-dependent manner: Implications in tumor blood flow
Compressed vessels bias red blood cell partitioning at bifurcations in a hematocrit-dependent manner: Implications in tumor blood flow
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DOI：
10.1073/pnas.2025236118
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发表时间：
2021-06-22
影响因子：
11.1
通讯作者：
Bernabeu, Miguel O.
中科院分区：
文献类型：
--
作者：
Enjalbert, Romain;Hardman, David;Bernabeu, Miguel O.
肿瘤微环境异常，并与肿瘤组织缺氧、免疫抑制和对治疗反应差有关。肿瘤中存在的一个重要异常是血管压迫。血管减压已被证明通过增强和更均匀的氧合来提高动物模型的存活率。然而，我们对肿瘤减压与改善肿瘤氧合作用的生物物理机制的认识是有限的。在这项研究中，我们提出了一个计算模型来研究血管压缩对肿瘤血管网络中红细胞（RBC）动力学的影响。我们的研究结果表明，血管压缩可以改变红细胞分配在分叉的红细胞压积依赖性和流量无关的方式。我们确定红细胞聚焦由于跨流线迁移的机制负责和表征的时空恢复动态控制下游分区。基于这些知识，我们制定了一个降阶模型，这将有助于未来的研究，以阐明这些影响如何在整个血管网络的水平传播。这些发现有助于了解肿瘤血管网络中血液稀释和药物实体瘤减压后氧均质化的机制。
The tumor microenvironment is abnormal and associated with tumor tissue hypoxia, immunosuppression, and poor response to treatment. One important abnormality present in tumors is vessel compression. Vessel decompression has been shown to increase survival rates in animal models via enhanced and more homogeneous oxygenation. However, our knowledge of the biophysical mechanisms linking tumor decompression to improved tumor oxygenation is limited. In this study, we propose a computational model to investigate the impact of vessel compression on red blood cell (RBC) dynamics in tumor vascular networks. Our results demonstrate that vessel compression can alter RBC partitioning at bifurcations in a hematocrit-dependent and flow rate-independent manner. We identify RBC focusing due to cross-streamline migration as the mechanism responsible and characterize the spatiotemporal recovery dynamics controlling downstream partitioning. Based on this knowledge, we formulate a reduced-order model that will help future research to elucidate how these effects propagate at a whole vascular network level. These findings contribute to the mechanistic understanding of hemodilution in tumor vascular networks and oxygen homogenization following pharmacological solid tumor decompression.