Cold atmospheric pressure plasma as a tool to control the proliferation of various mammalian cells including human mesenchymal stem cells for regenerative medicine

Cell proliferation is one of the most critical processes for development, tissue regen-eration, and wound healing, and is tightly linked with cell differentiation and migration. Also, the regulation of cell proliferation is essential for appropriate tissue regeneration and improved culture system, which requires an effective control tool for cell proliferation both in vivo and in vitro. Recently, cold atmospheric pressure plasma (CAP) has been shown to have considerable effects on cell proliferation that have been attributed to the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Many studies on CAP application suggest that CAP can be developed as an efficient tool to activate proliferation in vitro for personalized cell therapies and in vivo for wound healing. In this review, we discuss how CAP has been applied to control proliferation in various mammalian cells and its molecular mechanisms for biomedical applications. In our study, we demonstrated that nitric oxide (NO) from CAP is the major factor for activating the proliferation of human mesenchymal stem cells. When exposed to CAP, many different types of human cells displayed highly increased expression of cytokines and growth factors both in vitro and in vivo, strongly suggesting that common mechanisms and components are involved in CAP-induced cell proliferation. Furthermore, CAP induced epigenetic modifications in human mesen-chymal stem cells to boost the expression of cytokines and growth factors, thereby promoting cell proliferation. Further studies are needed to verify that NO of the CAP and epigenetic modifications are the common mechanism of action of CAP in culture and in wounded tissues. In addition, the molecular mechanism of the epigenetic modifications induced by CAP treatment should be inves-tigated to develop CAP as an applicable tool for regenerative medicine and wound healing.