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Experimental and mathematical modelling of magnetically labelled mesenchymal stromal cell delivery
Journal of The Royal Society Interface ( IF 3.7 ) Pub Date : 2021-02-17 , DOI: 10.1098/rsif.2020.0558
E F Yeo 1 , H Markides 2, 3 , A T Schade 3 , A J Studd 3 , J M Oliver 1 , S L Waters 1 , A J El Haj 2, 3
Affiliation  

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 combined in vitro experimental 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 targeting in vivo. In vitro MSCs 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 future in vitro experiments to quantify this effect.



中文翻译:

磁性标记间充质基质细胞递送的实验和数学模型

干细胞疗法的一个关键挑战是将治疗细胞输送到修复部位。磁性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 (MSCs) 的磁性靶向。本研究旨在 (i) 证明磁性标记在 MSC 递送中的潜力,(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力以及关于体内细胞靶向的预测。体外MSC 与磁性纳米颗粒一起培养,并与 RBC 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带有 RBC 的磁性标记 MSC 的流动。数值模拟表明与实验结果的定性一致,表明更强的磁场和更低水平的红细胞可以更好地捕获。我们还利用数学模型对外渗的作用做出假设,并确定未来的体外实验以量化这种影响。

更新日期:2021-02-17
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