Mechanobiological conditioning of mesenchymal stem cells for enhanced vascular regeneration

Adult Male 0301 basic medicine 0303 health sciences Neovascularization, Physiologic Mesenchymal Stem Cells Mesenchymal Stem Cell Transplantation Biomechanical Phenomena Mice Young Adult 03 medical and health sciences Ischemia Animals Humans Regeneration Female Receptors, Growth Factor Protein Kinase Inhibitors Signal Transduction
DOI: 10.1038/s41551-020-00674-w Publication Date: 2021-01-22T17:10:27Z
ABSTRACT
Using endogenous mesenchymal stem cells for treating myocardial infarction and other cardiovascular conditions typically results in poor efficacy, in part owing to the heterogeneity of the harvested cells and of the patient responses. Here, by means of high-throughput screening of the combinatorial space of mechanical-strain level and of the presence of particular kinase inhibitors, we show that human mesenchymal stem cells can be mechanically and pharmacologically conditioned to enhance vascular regeneration in vivo. Mesenchymal stem cells conditioned to increase the activation of signalling pathways mediated by Smad2/3 (mothers against decapentaplegic homolog 2/3) and YAP (Yes-associated protein) expressed markers that are associated with pericytes and endothelial cells, displayed increased angiogenic activity in vitro, and enhanced the formation of vasculature in mice after subcutaneous implantation and after implantation in ischaemic hindlimbs. These effects were mediated by the crosstalk of endothelial-growth-factor receptors, transforming-growth-factor-beta receptor type 1 and vascular-endothelial-growth-factor receptor 2. Mechanical and pharmacological conditioning can significantly enhance the regenerative properties of mesenchymal stem cells.
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