Abstract
Endothelial cells (ECs) play a major role in the healing process following angioplasty to inhibit excessive neointima. This makes the process of EC healing after injury, in particular EC migration in a stented vessel, important for recovery of normal vessel function. In that context, we present a novel particle-based model of EC migration and validate it against in vitro experimental data. We have developed a particle-based model of EC migration under flow conditions in an in vitro vessel with obstacles. Cell movement in the model is a combination of random walks and directed movement along the local flow velocity vector. For model calibration, a set of experimental data for cell migration in a similarly shaped channel has been used. We have calibrated the model for a baseline case of a channel with no obstacles and then applied it to the case of a channel with ridges on the bottom surface, representative of stent strut geometry. We were able to closely reproduce the cell migration speed and angular distribution of their movement relative to the flow direction reported in vitro. The model also reproduces qualitative aspects of EC migration, such as entrapment of cells downstream from the flow-disturbing ridge. The model has the potential, after more extensive in vitro validation, to study the effect of variation in strut spacing and shape, through modification of the local flow, on EC migration. The results of this study support the hypothesis that EC migration is strongly affected by the direction and magnitude of local wall shear stress.
Highlights
Endothelial cells (ECs) cover the inner surfaces of blood and lymph vessels and are necessary to ensure proper function
To study endothelial recovery and wound healing in stented vessels, we have developed an in silico model for EC migration under flow conditions
The best agreement for cell movement speed and the cell trajectory angular distribution between the model and cell migration in a flat channel without ridges was achieved for pchange = 0.075 per hour
Summary
Endothelial cells (ECs) cover the inner surfaces of blood and lymph vessels and are necessary to ensure proper function. If the layer of ECs is damaged or disrupted, smooth muscle cell (SMC) proliferation from the medial layer of the vessel wall into the lumen may occur. Recovery of ECs following injury is crucial to suppress the proliferation of SMCs (Iqbal et al 2013; Tahir et al 2014; Jukema et al 2012). If inhibition of SMC proliferation is delayed, excessive neointimal tissue growth narrows the lumen, restricting blood flow Jukema et al (2012). One important case is the growth of neointimal tissue in a coronary vessel after stenting. Stenting is a frequently used coronary intervention, consisting of the implantation of a metal mesh called a stent into the vessel to restore the lumen, following development of coronary atherosclerosis. The stent struts and the balloon are used to deploy it partly or completely remove the
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