Centre for Medical Informatics, Usher Institute, The University of Edinburgh, Edinburgh EH16 4UX, United Kingdom.
School of Engineering, Institute for Multiscale Thermofluids, The University of Edinburgh, Edinburgh EH9 3FD, United Kingdom;
Proc Natl Acad Sci U S A. 2021 Jun 22;118(25). doi: 10.1073/pnas.2025236118. Epub 2021 Jun 17.
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.
肿瘤微环境异常，与肿瘤组织缺氧、免疫抑制和治疗反应差有关。肿瘤中存在的一个重要异常是血管受压。研究表明，血管减压通过增强和更均匀的氧合作用，增加动物模型的存活率。然而，我们对将肿瘤减压与改善肿瘤氧合联系起来的生物物理机制的了解是有限的。在这项研究中，我们提出了一个计算模型来研究血管受压对肿瘤血管网络中红细胞（RBC）动力学的影响。我们的结果表明，血管受压可以以依赖于血细胞比容和独立于血流速率的方式改变分支处的 RBC 分配。我们确定由于流线交叉迁移导致的 RBC 聚焦是造成这种情况的原因，并描述了控制下游分配的时空恢复动力学。基于这些知识，我们提出了一个简化模型，将有助于未来的研究阐明这些影响在整个血管网络水平上是如何传播的。这些发现有助于深入了解肿瘤血管网络中的血液稀释以及药物治疗后实体肿瘤减压引起的氧合均匀化。
