Platelets Facilitate Wound Healing by Mitochondrial Transfer and Reducing Oxidative Stress in Endothelial Cells

Abstract

As a critical member in wound healing, vascular endothelial cells (ECs) impaired under high levels of reactive oxygen species (ROS) would hamper neovascularization. Mitochondria transfer can reduce intracellular ROS damage under pathological condition. Meanwhile, platelets can release mitochondria and alleviate oxidative stress. However, the mechanism by which platelets promote cell survival and reduce oxidative stress damage has not been clarified. Here, first, we selected ultrasound as the best method for subsequent experiments by detecting the growth factors and mitochondria released from manipulation platelet concentrates (PCs), as well as the effect of manipulation PCs on the proliferation and migration of HUVECs. Then, we found that sonicate platelet concentrates (SPC) decreased the level of ROS in HUVECs treated with hydrogen peroxide in advance, increased mitochondrial membrane potential, and reduced apoptosis. By transmission electron microscope, we saw that two kinds of mitochondria, free or wrapped in vesicles, were released by activated platelets. In addition, we explored that platelet-derived mitochondria were transferred to HUVECs partly by means of dynamin-dependent clathrin-mediated endocytosis. Consistently, we determined that platelet-derived mitochondria reduced apoptosis of HUVECs caused by oxidative stress. What is more, we screened survivin as the target of platelet-derived mitochondria via high-throughput sequencing. Finally, we demonstrated that platelet-derived mitochondria promoted wound healing in vivo. Overall, these findings revealed that platelets are important donors of mitochondria, and platelet-derived mitochondria can promote wound healing by reducing apoptosis caused by oxidative stress in vascular endothelial cells. And survivin is a potential target. These results further expand the knowledge of the platelet function and provide new insights into the role of platelet-derived mitochondria in wound healing.

iPSC-derived megakaryocytes and platelets accelerate wound healing and angiogenesis.

“…In addition, the animal models in which treatment and analysis are initiated simultaneously with the preparation of skin injury do not replicate the inflammatory conditions caused by infection in chronic wounds. Finally, despite previous reports that platelet-derived EVs [35] and mitochondria [36] promote wound healing, these factors were not investigated in this study. These issues need to be considered in future research.…”

Mitochondria Transplantation Promotes Corneal Epithelial Wound Healing

“…Although the precise molecular mechanisms that underlie the effects of mitochondrial transfer are not fully defined, mitochondrial transfer was shown to restore cellular bioenergetics and alter the metabolic state of recipient cells. 10 , 13 , 14 , 17 , 39 – 49 In CECs, transfer of mitochondria from MSCs via tunneling nanotubes was shown to improve cell survival under conditions of oxidative stress. Mechanistically, the effect of the transferred mitochondria was correlated to increased respiration and reduced oxidative stress signaling such as NFkB.…”

“…Interestingly, lateral transfer of mitochondria between cells occurs in various cell types under stress conditions, and in some cases has been shown to facilitate wound healing. 10 – 17 In the context of corneal repair, topical application of mesenchymal stem cells (MSCs) to the corneal surface induced mitochondrial transfer to corneal epithelial cells (CECs) and facilitated wound healing in rabbits following chemical injury. 18 This observation underscores the potential of mitochondrial transfer as a therapeutic strategy for enhancing corneal wound healing.…”

Pharmacotherapy for Keloids and Hypertrophic Scars

“…Thus, autologous platelet-based concentrates represent increasingly popular adjuncts to a variety of medical, surgical and aesthetic interventions. Their beneficial potential rests on the ability to deliver a high concentration of growth factors to the target tissues [356]. In addition, platelets are important donors of mitochondria, and platelet-derived mitochondria can promote wound healing by reducing apoptosis caused by oxidative stress in vascular endothelial cells [357].…”