Recent progress in atmospheric plasmas has led to the creation of cold plasmas with ion temperature close to room temperature. This paper outlines recent progress in understanding of cold plasma physics as well as application of cold atmospheric plasma (CAP) in cancer therapy. Varieties of novel plasma diagnostic techniques were developed recently in a quest to understand physics of CAP. It was established that the streamer head charge is about 108 electrons, the electrical field in the head vicinity is about 107 V/m, and the electron density of the streamer column is about 1019 m−3. Both in-vitro and in-vivo studies of CAP action on cancer were performed. It was shown that the cold plasma application selectively eradicates cancer cells in-vitro without damaging normal cells and significantly reduces tumor size in-vivo. Studies indicate that the mechanism of action of cold plasma on cancer cells is related to generation of reactive oxygen species with possible induction of the apoptosis pathway. It is also shown that the cancer cells are more susceptible to the effects of CAP because a greater percentage of cells are in the S phase of the cell cycle.

The interaction of the cold atmospheric plasma jet with fibroblast cells was studied. Plasma jet was initiated in the helium flow blowing through the syringe by application of high ac voltage to the discharge electrodes. The plasma jet had a length of $5\mathrm{cm}$ and a diameter of $1.5–2\mathrm{mm}$ in ambient air. Treatment of cells with plasma jet resulted in decreasing of cell migration rate, cell detachment, and appearance of “frozen” cells, while treatment with helium flow (no plasma) resulted in appearance of frozen cells only. A variety of cellular responses was explained by different intensities of treatment.

Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating S-phase damage, is enhanced specifically within CAP treated cells in the S phase of the cell cycle. Together with a significant decrease in EdU-incorporation after CAP, these data suggest that tumorigenic cancer cells are more susceptible to CAP treatment.

Mice lacking syndecan-1 are viable, fertile and have morphologically normal skin, hair and ocular surface epithelia. While studying the response of these mice to corneal epithelial and skin wounding, we identified defects in epithelial cell proliferation and regulation of integrin expression. mRNA profiling of corneal epithelial tissues obtained from wild-type and syndecan-1^-/- mice suggest that these defects result from differences in overall gene transcription. In the cornea, syndecan-1^-/- epithelial cells migrate more slowly, show reduced localization of α9 integrin during closure of wounds and fail to increase their proliferation rate 24 hours after wounding. In the skin, we did not document a migration defect after full thickness wounds but did observe cell proliferation delays and reduced localization of α9 integrin in the syndecan-1^-/- epidermis after dermabrasion. Despite increased cell proliferation rates in the uninjured syndecan-1^-/- epidermis and the corneal epithelium, morphologically normal epithelial thickness is maintained prior to injury; however, wounding is accompanied by prolonged hypoplasia in both tissues. Analyses of integrin protein levels in extracts from full thickness skin, revealed increased levels of α3 and α9 integrins both prior to injury and after hair removal in syndecan-1^-/- mice but no increase 2 days after dermabrasion. These data for the first time show involvement of α9 integrin in skin wound healing and demonstrate essential roles for syndecan-1 in mediating cell proliferation and regulation of integrin expression in normal and wounded epithelial tissues.

Mock cataract surgery provides a unique ex vivo model for studying wound repair in a clinically relevant setting. Here wound healing involves a classical collective migration of the lens epithelium, directed at the leading edge by an innate mesenchymal subpopulation of vimentin-rich repair cells. We report that vimentin is essential to the function of repair cells as the directors of the wound-healing process. Vimentin and not actin filaments are the predominant cytoskeletal elements in the lamellipodial extensions of the repair cells at the wound edge. These vimentin filaments link to paxillin-containing focal adhesions at the lamellipodial tips. Microtubules are involved in the extension of vimentin filaments in repair cells, the elaboration of vimentin-rich protrusions, and wound closure. The requirement for vimentin in repair cell function is revealed by both small interfering RNA vimentin knockdown and exposure to the vimentin-targeted drug withaferin A. Perturbation of vimentin impairs repair cell function and wound closure. Coimmunoprecipitation analysis reveals for the first time that myosin IIB is associated with vimentin, linking vimentin function in cell migration to myosin II motor proteins. These studies reveal a critical role for vimentin in repair cell function in regulating the collective movement of the epithelium in response to wounding.