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流体切应力对骨细胞和癌细胞增殖及分布的影响。

The Influence of Fluid Shear Stress on Bone and Cancer Cells Proliferation and Distribution.

机构信息

Department of Civil, Construction and Environmental Engineering, North Dakota State University, Fargo, ND, USA.

出版信息

Ann Biomed Eng. 2023 Jun;51(6):1199-1215. doi: 10.1007/s10439-022-03123-8. Epub 2023 Jan 2.

DOI:10.1007/s10439-022-03123-8
PMID:36593306
Abstract

We investigated the potential correlation between the fluid shear stress and the proliferation of bone prostate cancer cells on the surface of nanoclay-based scaffolds in a perfusion bioreactor. Human mesenchymal stem cells (hMSCs) were seeded on the scaffolds to initiate bone growth. After 23 days, prostate cancer cells (MDAPCa2b) were cultured on top of the osteogenically differentiated hMSCs. The scaffolds were separated into two groups subjected to two distinct conditions: (i) static (no flow); and (ii) dynamic (with flow) conditions to recapitulate bone metastasis of prostate cancer. Based on measured data, Computational Fluid Dynamics (CFD) models were constructed to determine the velocity and shear stress distributions on the scaffold surface. Our experimental results show distinct differences in the growth pattern of hMSCs and MDAPCa2b cells between the static and dynamic conditions. Our computational results further suggest that the dynamic flow leads to drastic change in cell morphology and tumorous distribution. Our work points to a strong correlation between tumor growth and local interstitial flows in bones.

摘要

我们研究了在灌注生物反应器中,纳米粘土基支架表面的流体切应力与前列腺癌细胞增殖之间的潜在相关性。将人骨髓间充质干细胞 (hMSC) 接种在支架上以启动骨生长。23 天后,在成骨分化的 hMSC 上培养前列腺癌细胞 (MDAPCa2b)。将支架分为两组,分别处于两种不同的条件下:(i)静态(无流动);和(ii)动态(有流动),以再现前列腺癌的骨转移。根据测量数据,构建了计算流体动力学 (CFD) 模型,以确定支架表面的速度和剪切应力分布。我们的实验结果表明,静态和动态条件下 hMSC 和 MDAPCa2b 细胞的生长模式有明显差异。我们的计算结果进一步表明,动态流动会导致细胞形态和肿瘤分布的剧烈变化。我们的工作表明,肿瘤生长与骨骼内局部间质流之间存在很强的相关性。

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本文引用的文献

1
Prostate Cancer Phenotype Influences Bone Mineralization at Metastasis: A Study Using an In Vitro Prostate Cancer Metastasis Testbed.前列腺癌表型影响转移灶的骨矿化:一项使用体外前列腺癌转移试验台的研究。
JBMR Plus. 2019 Dec 30;4(2):e10256. doi: 10.1002/jbm4.10256. eCollection 2020 Feb.
2
A multiscale computational fluid dynamics approach to simulate the micro-fluidic environment within a tissue engineering scaffold with highly irregular pore geometry.采用多尺度计算流体动力学方法模拟具有高度不规则孔隙几何形状的组织工程支架内的微流体环境。
Biomech Model Mechanobiol. 2019 Dec;18(6):1965-1977. doi: 10.1007/s10237-019-01188-4. Epub 2019 Jun 14.
3
In vitro design of mesenchymal to epithelial transition of prostate cancer metastasis using 3D nanoclay bone-mimetic scaffolds.
使用 3D 纳米黏土仿生骨支架在体外设计前列腺癌转移的间质上皮转化。
J Tissue Eng Regen Med. 2018 Mar;12(3):727-737. doi: 10.1002/term.2492. Epub 2017 Oct 4.
4
Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling.间质液流动通过CXCR4/CXCL12和MEK/ERK信号通路增加肝癌细胞侵袭。
PLoS One. 2015 Nov 11;10(11):e0142337. doi: 10.1371/journal.pone.0142337. eCollection 2015.
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Biomineralized hydroxyapatite nanoclay composite scaffolds with polycaprolactone for stem cell-based bone tissue engineering.用于基于干细胞的骨组织工程的生物矿化羟基磷灰石纳米粘土与聚己内酯复合支架
J Biomed Mater Res A. 2015 Jun;103(6):2077-101. doi: 10.1002/jbm.a.35342. Epub 2014 Oct 21.
6
Micro-computed tomography based computational fluid dynamics for the determination of shear stresses in scaffolds within a perfusion bioreactor.基于微计算机断层扫描的计算流体动力学用于确定灌注生物反应器内支架中的剪应力。
Ann Biomed Eng. 2014 May;42(5):1085-94. doi: 10.1007/s10439-014-0981-0. Epub 2014 Feb 4.
7
Vortex phenomena in sidewall aneurysm hemodynamics: experiment and numerical simulation.侧壁动脉瘤血流动力学中的涡流现象:实验与数值模拟。
Ann Biomed Eng. 2013 Oct;41(10):2157-70. doi: 10.1007/s10439-013-0811-9. Epub 2013 Apr 20.
8
Interstitial flow influences direction of tumor cell migration through competing mechanisms.间质流通过竞争机制影响肿瘤细胞迁移的方向。
Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11115-20. doi: 10.1073/pnas.1103581108. Epub 2011 Jun 20.
9
Shear stress induces osteogenic differentiation of human mesenchymal stem cells.切应力诱导人骨髓间充质干细胞的成骨分化。
Regen Med. 2010 Sep;5(5):713-24. doi: 10.2217/rme.10.60.
10
Mechanisms of bone metastasis.骨转移的机制。
N Engl J Med. 2004 Apr 15;350(16):1655-64. doi: 10.1056/NEJMra030831.