Single-cell characterization of deformation and dynamics of mesenchymal stem cells in microfluidic systems: A computational study

Understanding the homing dynamics of individual mesenchymal stem cells (MSCs) in physiologically relevant microenvironments is crucial for improving the efficacy of MSC-based therapies for therapeutic and targeting purposes. This study investigates the passive homing behavior of individual MSCs in micropores that mimic interendothelial clefts through predictive computational simulations informed by previous microfluidic experiments. Initially, we quantified the size-dependent behavior of MSCs in micropores and elucidated the underlying mechanisms. Subsequently, we analyzed the shape deformation and traversal dynamics of each MSC. In addition, we conducted a systematic investigation to understand how the mechanical properties of MSCs impact their traversal process. We considered geometric and mechanical parameters, such as reduced cell volume, cell-to-nucleus diameter ratio, and cytoskeletal prestress states. Furthermore, we quantified the changes in the MSC traversal process and identified the quantitative limits in their response to variations in micropore length. Taken together, the computational results indicate the complex dynamic behavior of individual MSCs in the confined microflow. This finding offers an objective way to evaluate the homing ability of MSCs in an interendothelial-slit-like microenvironment.