Combining in silico and in vitro models to inform cell seeding strategies in tissue engineering.
Combining in silico and in vitro models to inform cell seeding strategies in tissue engineering.
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DOI：
10.1098/rsif.2019.0801
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发表时间：
2020-03-01
期刊：
影响因子：
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通讯作者：
Shipley, R J
中科院分区：
文献类型：
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作者：
Coy, R;Al-Badri, G;Shipley, R J
治疗细胞在工程化组织中的种植密度影响细胞存活和血管形成。过高的种子细胞密度会导致死亡增加，从而浪费有价值的细胞，而较低的种子细胞密度可能不能为体内的组织提供足够的支持，从而降低疗效。此外，治疗细胞在低氧环境中产生生长因子提供了一种产生生长因子梯度的方法，这对血管形成非常重要，但低氧也会导致不必要的细胞死亡。这是一个复杂的问题，需要计算模型和实验相结合。在这里，我们提出了一个利用体外数据参数化的时空数学模型，该模型能够模拟工程组织中治疗细胞群、氧浓度和血管内皮生长因子(VEGF)浓度之间的相互作用。对胶原神经修复结构的模拟表明，特定的种子细胞密度和种子细胞的不均匀空间分布可以提高细胞存活率和血管内皮生长因子梯度的产生。这些预测现在可以通过有针对性的实验来检验。
The seeding density of therapeutic cells in engineered tissue impacts both cell survival and vascularization. Excessively high seeded cell densities can result in increased death and thus waste of valuable cells, whereas lower seeded cell densities may not provide sufficient support for the tissue in vivo, reducing efficacy. Additionally, the production of growth factors by therapeutic cells in low oxygen environments offers a way of generating growth factor gradients, which are important for vascularization, but hypoxia can also induce unwanted levels of cell death. This is a complex problem that lends itself to a combination of computational modelling and experimentation. Here, we present a spatio-temporal mathematical model parametrized using in vitro data capable of simulating the interactions between a therapeutic cell population, oxygen concentrations and vascular endothelial growth factor (VEGF) concentrations in engineered tissues. Simulations of collagen nerve repair constructs suggest that specific seeded cell densities and non-uniform spatial distributions of seeded cells could enhance cell survival and the generation of VEGF gradients. These predictions can now be tested using targeted experiments.