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
AUTHORS (15)
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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