Non-thermal atmospheric pressure plasma is an excellent tool to activate proliferation in various mesoderm-derived human adult stem cells

Abstract

Adult stem cells are capable of self-renewal and differentiation into specific cell types in tissues and have high potential for stem cell therapy. Mesenchymal and hematopoietic stem cells are easily attainable from the human body and have become applicable tools for adult stem cell therapy. However, there are still technical barriers for the application of mesenchymal and hematopoietic stem cells for therapy, such as the small number of cell populations, high risk of contamination, and loss of their stemness properties in vitro. In our previous study, we showed that non-thermal atmospheric pressure plasma (NTAPP) promoted the proliferation of adipose tissue-derived stem cells (ASCs) by 1.6-fold on average, while maintaining their stemness. Here, we examined the feasibility of NTAPP as a tool to activate the proliferation of mesenchymal and hematopoietic stem cells in vitro without affecting their stem cell characteristics. NTAPP increased the proliferation of bone marrow-derived stem cells (BM-MSCs) and hematopoietic stem cells (HSCs) by 1.8- and 2-fold, respectively, when compared to that of untreated cells. As observed in ASCs, NTAPP exposure also activated the expression of stem cell-specific surface markers, CD44 and CD105, by 5-fold in BM-MSCs, when compared to that in unexposed control cells in a low glucose medium with a low concentration of basic fibroblast growth factor (b-FGF). In addition, NTAPP exposure highly augmented the mRNA expression of well-known pluripotent genes for stemness, such as Oct4, Sox2, and Nanog in ASCs and BM-MSCs when compared to that in unexposed control cells. When cell cycle progression was examined, the G1-S shift was accelerated, and expression of PCNA was increased in NTAPP-exposed ASCs when compared to that in untreated control cells, suggesting that NTAPP activated G1-S transition. Taken together, these results demonstrated that NTAPP activated the proliferation of various mesodermal-derived human adult stem cells by accelerating the G1-S transition while maintaining their pluripotency and stemness, strongly suggesting that NTAPP can be an efficient tool for expanding the population of various adult stem cells in vitro for medical applications.