Experimental and mathematical modelling of magnetically labelled mesenchymal stromal cell delivery.

Experimental and mathematical modelling of magnetically labelled mesenchymal stromal cell delivery.
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磁性标记间充质基质细胞递送的实验和数学模型。

DOI:
10.1098/rsif.2020.0558
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发表时间:
2021
期刊:
Journal of the Royal Society, Interface
影响因子:
--
通讯作者:
Yeo EF
Yeo EF
中科院分区:
--
文献类型:
--
作者:
Yeo EF

文献摘要

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干细胞疗法的一个关键挑战是将治疗性细胞输送到修复部位。磁靶向已被提议作为更有效地定义临床递送部位的平台。在本文中,我们使用体外实验和数学建模相结合的方法来探索使用外部磁体标记磁性纳米颗粒的间充质基质细胞(MSC)的磁性靶向。这项研究的目的是(i)证明磁标记用于MSC递送的潜力,(ii)检查红细胞(RBC)对MSC捕获功效的影响,以及(iii)强调数学模型如何提供对治疗机制的洞察和对体内细胞靶向的预测。在体外,MSC与磁性纳米颗粒一起培养,并与RBC一起在外部磁体上循环。针对不同的磁场强度和RBC百分比测量细胞捕获功效。我们使用2D连续数学模型来表示具有RBC的磁性标记的MSC的流动。数值模拟表明与实验结果的定性一致性,显示出更好的捕获与更强的磁场和更低水平的红细胞。我们还利用数学模型,使外渗的作用的假设,并确定未来的体外实验,以量化这种效果。
A key challenge for stem cell therapies is the delivery of therapeutic cells to the repair site. Magnetic targeting has been proposed as a platform for defining clinical sites of delivery more effectively. In this paper, we use a combinedin vitroexperimental and mathematical modelling approach to explore the magnetic targeting of mesenchymal stromal cells (MSCs) labelled with magnetic nanoparticles using an external magnet. This study aims to (i) demonstrate the potential of magnetic tagging for MSC delivery, (ii) examine the effect of red blood cells (RBCs) on MSC capture efficacy and (iii) highlight how mathematical models can provide both insight into mechanics of therapy and predictions about cell targetingin vivo. In vitroMSCs are cultured with magnetic nanoparticles and circulated with RBCs over an external magnet. Cell capture efficacy is measured for varying magnetic field strengths and RBC percentages. We use a 2D continuum mathematical model to represent the flow of magnetically tagged MSCs with RBCs. Numerical simulations demonstrate qualitative agreement with experimental results showing better capture with stronger magnetic fields and lower levels of RBCs. We additionally exploit the mathematical model to make hypotheses about the role of extravasation and identify futurein vitroexperiments to quantify this effect.