Mechanobiological Conditioning of Mesenchymal Stem Cells Enhances Therapeutic Angiogenesis by Inducing a Hybrid Pericyte-Endothelial Phenotype

Stem cell therapies have great promise for revolutionizing treatments for cardiovascular disease and other disorders but have not yet achieved their potential due to poor efficacy and heterogeneity in patient response. Here, we used a novel high throughput screening system to optimize the conditioning of mesenchymal stem cells using a combinatorial set of biochemical factors, pharmacological inhibitors and biomechanical forces. Our studies revealed that a combination of specific kinase inhibitors and a complex mechanical strain waveform dramatically increased the population of mesenchymal stem cells that express markers for both pericytes and endothelial cells. These mechanically and pharmacologically conditioned mesenchymal stem cells had superior properties in enhancing endothelial tube formation, production of angiogenic growth factors and induction of angiogenesis following implantation. Overall, our work supports that combinatorial optimization of mechanical conditioning and pharmacological treatments can significantly enhance the regenerative properties of mesenchymal stem cells.