In addition, nucleocytoplasmic shuttling regulates FoxO activity. differentiation, understanding the underlying molecular mechanisms involved will provide important new insights into NBP-induced stem cell differentiation for tissue engineering. 1. Redox Homeostasis in Stem Cell Differentiation The focus of tissue engineering is usually regenerating damaged tissues through the restoration, maintenance, and improvement of tissue function . For example, in bone D609 tissue, the crucial size of bone defects, which lies beyond the spontaneous regeneration capacity of a patient and thus requires surgical invention, has guided research into bone tissue engineering-based therapeutics . Stem cells are the crucial cell sources in tissue engineering that possess the characteristics of self-renewal and potential to differentiate into multiple cell types for the repair and/or regeneration of defective tissues and organs, such as the bone, cartilage, heart, neurons, and spinal cord [3C7]. To induce stem cell differentiation, growth factors are the most commonly used technique. Other techniques are also being analyzed, such as the electromagnetic field, vibration, radiation, heat shock, and oxidative stress [8C17]. Scaffolds provide a framework for stem cells to migrate to, attach to, and specialize on . However, the low efficiency of growth and differentiation of stem cells is usually resulting in attempts to develop new methods to improve their characteristics. Since stem cells are an essential part of tissue regeneration, considerable research has been conducted around the factors regulating stem cell self-renewal and differentiation. Reactive oxygen species (ROS), the highly chemically reactive byproducts of aerobic metabolism, Rabbit Polyclonal to PLG are important mediators in stem cell biology [18, 19]. Changes in ROS levels can be used to monitor the balance of stem cell self-renewal and differentiation. Although high levels of ROS have long been suggested to be detrimental to mediating oxidative stress, mounting experimental evidence indicates that this physiological levels of ROS are involved in the maintenance of intracellular reduction-oxidation (redox) homeostasis and various cellular signaling pathways . ROS in redox homeostasis plays a pivotal role in the maintenance of stem cell self-renewal with low levels of ROS, whereas in differentiated stem cells, ROS D609 is usually accumulated . For example, a quantitative study comparing human embryonic stem cells (ESC) with their differentiated descendants has shown that ESC are characterized by a lower ROS level, while differentiated cells contain more oxidative species. However, biochemical normalization of the ROS level to cell volume/protein indicates that all cell types maintain a similar intracellular redox of the ROS level as a measure of intracellular redox balance . ROS are also involved in transmission transduction cascades in enhancing the differentiation of ESC toward the cardiomyogenic and vascular cell lineage . These findings imply that redox signaling plays a crucial role in modulating the fate of D609 stem cells. Therefore, it is possible that manipulating the exogenous ROS donor tool could activate intracellular redox-dependent signaling to maintain stem cell differentiation. 2. Nonthermal Biocompatible Plasma (NBP) Nonthermal biocompatible plasma (NBP) (or plasma) is usually produced by applying a sufficiently high-voltage electric field across the discharge space to initiate a breakdown of gas at atmospheric pressure . When NBP is usually generated, the major components of charged particles, neutral gas species, reactive species, electric field, and radiation are produced. NBP was first employed in antimicrobial applications, because it produces a variety of biotoxic brokers that include reactive species, UV radiation, and charged particles. Since then, NBP has come to be extensively analyzed in other applications in the biomedical field, including in sterilization, malignancy cell apoptosis, wound healing, blood coagulation, and teeth whitening [25C31], which has made NBP a encouraging tool for biomedical use. An increasing quantity of studies have shown the role of NBP in tissue engineering on the surface modification of biomaterials [32C34] and as an exogenous stimulator that directly induces stem cell proliferation and differentiation [35C40]. In this section, NBP devices and their characteristics will be summarized and analyzed so as to provide a more detailed concept of NBP production and composition. 2.1. Classification of NBP Devices NBP devices for stem cell differentiation can be broadly classified into two major groups: plasma jet and dielectric barrier discharge (DBD) D609 plasma. Physique 1 shows an example schematic of a plasma jet and DBD device produced in our research center. The basic structure of the plasma jet type consists of an inner high-voltage electrode, which is usually coupled with the.