Platelets Promote Pro-Angiogenic Activity of Mesenchymal Stem Cells Via Mitochondrial Transfer and Metabolic Reprogramming

Platelets are known to enhance the wound-healing activity of mesenchymal stem cells (MSCs). However, the mechanism by which platelets improve MSC therapeutic potential has not been elucidated. Here we provide evidence that, upon their activation, platelets transfer respiratory-competent mitochondria to MSCs. We found that this process boosts the therapeutic efficacy of MSCs following their engraftment in a mouse wound healing injury model. By combining in vitro and in vivo experiments, we demonstrated that platelet-derived mitochondria promote the pro-angiogenic activity of MSCs through their metabolic remodeling. Notably, we show that activation of the de novo fatty acid synthesis pathway is required for the increased secretion of pro-angiogenic factors by platelet-preconditioned MSCs. These results reveal a new mechanism by which platelets potentiate properties of MSCs throughout mitochondria transfer and metabolic conversion of MSCs.