Exosomes derived from human dental pulp stem cells increase flap survival with ischemia-reperfusion injuries

Aim: To investigate the effect of hDPSC-Exos in flap I/R injury, a condition in which tissue damage increases after blood flow is restored to the flap after ischemia. Materials & methods: HUVECs were used to investigate the influences and mechanisms of hDPSC-Exos on cell proliferation and migration. A rat model was established to verify the role of hDPSC-Exos in flap I/R injuries in vivo. Results: hDPSC-Exos promoted the proliferation, migration and tube formation of HUVECs in a dose-dependent way by activating PI3K/AKT signaling pathway, and improved the survival and microvessel density of the flap and suppressed epithelial cell apoptosis. Conclusion: hDPSC-Exos can enhance flap repair after I/R injury. This process may be mediated by the activation of PI3K/AKT signaling pathway. Plain language summarySkin flap transplantation is one of the most important methods of repairing refractory wounds and organ reconstruction. I/R injury and insufficiency of neovascularization significantly affect the survival of flaps. Human dental pulp stem cells (hDPSCs) are a type of mesenchymal stem cells (MSCs) present in dental pulp tissue that have attracted increasing attention. They can play a repair role in a variety of ischemic injuries and neovascularization. Exosomes are important paracrine mediators between MSCs and target cells, containing a variety of proteins, mRNA and miRNA. Recent studies have shown that some exosomes derived from MSCs can improve I/R injury, promote angiogenesis and inhibit apoptosis. This study confirmed that hDPSC-Exos could promote the proliferation, migration and tubule formation of vein endothelial cells in a dose-dependent manner. Inhibition of PI3K/AKT signaling pathway can reduce the above promoting effects, suggesting that these processes may depend on the activation of PI3K/AKT signaling pathway. In the rat model, hDPSC-Exos can significantly improve the survival rate and microvessel density of flaps, and inhibit epithelial cell apoptosis.