It is also known that atherosclerosis and defective nutrition can delay or jeopardize the repair process. The options available today to care for acute or chronic lesions are numerous but at the same time, several factors work against the repair/regeneration process. According to the most up to date findings, normal wound repair after tissue injury follows a closely regulated sequence of events including the MDV3100 activation and proliferation of fibroblastic-like cells. In pathological situations the normal stages are altered and those processes continue inducing excessive accumulation of extracellular matrix. In view of these considerations, medical tools able to induce transient activation of fibroblast-like cells could be useful in promoting healing of lesions without inflammation and scarring. In the present study we have demonstrated that nonthermal atmospheric pressure plasma ionizing helium gas mixed with air generates active chemical species that tune the activation of two fibroblast-like cell populations by inducing intracellular ROS. For decades ROS have been considered accidental byproducts of oxygen metabolism having detrimental effects on cell survival. More recent investigations have however uncovered the dual nature of ROS and their role in sustaining normal biological functions. On the one hand, higher than normal ROS levels cause irreversible damage to cellular organelles, membrane, proteins and DNA; they have also been implicated in ageing, cancer, and neurodegenerative diseases. On the other, cells have evolved mechanisms such as antioxidant enzymes to modulate intracellular ROS levels. Thus, at low/moderate concentrations ROS activate the intracellular signaling pathways resulting in production of soluble factors involved in cell growth and proliferation. ROS generated in human HSCs and ISEMFs by plasma exposure were found here to be characterized by lower concentrations and shorter half-lives with respect to H2O2 induced ROS. The transient increase in ROS levels spared cells early markers of apoptosis such as the decrease in the mitochondrial membrane potential and the externalization of phosphatidylserine, an important recognition signal for macrophage activation and subsequent engagement of the inflammatory cascade. On the contrary, higher levels of ROS induced in HSCs and ISEMFs by incubation with 20 mMH 2O2 resulted in mitochondrial membrane damage and early cellular death. For sure, cellular damage could be avoided by lower concentrations of H2O2.