Non-thermal dielectric barrier discharge plasma (NT-Plasma) is a relatively new physics-based technology. Although there are few reports concerning the application of this technology to biological sciences, it is known that NT-plasma influences cell function mainly through activation of reactive oxygen and nitrogen species (ROS/RNS) signaling pathways. In collaboration with the Drexel Plasma Institute, arguably the foremost experts in the field of plasma physics in the United States, we propose to use NT-plasma as a tool to specifically manipulate cellular redox to promote MSC commitment and differentiation. The proposed study is based on recent observations that the NT-Plasma system promotes reactive oxygen species generation enhances development of embryonic structures and initiates the expression of many genes linked to cell differentiation. The first Specific Aim is to delineate the mechanism by which NT-Plasma generated ROS/RNS promotes MSC proliferation, commitment and differentiation;while simultaneously developing the NT-Plasma device for this application. We will test the hypothesis that NT-Plasma enhances stem cell differentiation along chondrogenic, endothelial and osteogenic lineages. Moreover, that this effect is mediated via ROS/RNS dependent signaling pathways that serve to influence the cell's oxidative state. To test this hypothesis, first, we will define the conditions that permit NT-Plasma to regulate the oxidative state of the cell. At the same time, we will fine tune the NT-Plasma system modulating the length of treatment, times of treatment and amplitude and discharge parameters. We will measure ROS and RNS, the redox status of the cells, the expression and activity of antioxidant proteins, as well as responsive signaling pathways. The second Specific Aim is to determine how NT-Plasma advances differentiation of progenitor cells in two model systems, an endochondral ossification system and a tissue engineered vascular tissue allograft. We propose to test the hypothesis that NT-Plasma positively influences stem cell commitment and differentiation in vivo. Each system provides a unique opportunity to evaluate the potential and feasibility of NT plasma treatment to enhance tissue healing and replacement, while at the same time gaining valuable understanding of the resulting signaling networks. If the goals of this application are successfully achieved, then the knowledge gained in development of NT-Plasma technology will be of transformative scientific and clinical importance. NT-Plasma's ability to amplify stem cell function will be an invaluable tool for tissue engineering and regenerative medicine in general, and will provide new insights into the basic biology of ROS signaling in stem cell biology.

Public Health Relevance

The purpose of this project is to explore and develop biological applications of Non-Thermal Plasma for use in tissue engineering and regenerative medicine. Our preliminary studies and other published reports indicate that this new technology can significantly influence the fate of adult stem cells and promote their proliferation, commitment and differentiation. Results generated from the proposed studies will provide improved methods for tissue repair and regeneration with direct applicability to both clinical research and surgical procedures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB013011-02
Application #
8240982
Study Section
Special Emphasis Panel (ZRG1-BST-E (51))
Program Officer
Hunziker, Rosemarie
Project Start
2011-04-01
Project End
2015-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
2
Fiscal Year
2012
Total Cost
$347,168
Indirect Cost
$80,709
Name
Thomas Jefferson University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
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Liu, Chong; Dobrynin, Danil; Fridman, Alexander (2014) Uniform and non-uniform modes of nanosecond-pulsed dielectric barrier discharge in atmospheric air: fast imaging and spectroscopic measurements of electric field. J Phys D Appl Phys 47:252003
Yang, Yong; Cho, Young I; Friedman, Gary et al. (2011) Self-Organization and Migration of Dielectric Barrier Discharge Filaments in Argon Gas Flow. IEEE Trans Plasma Sci IEEE Nucl Plasma Sci Soc 39:2060-2061
Sensenig, Rachel; Kalghatgi, Sameer; Cerchar, Ekaterina et al. (2011) Non-thermal plasma induces apoptosis in melanoma cells via production of intracellular reactive oxygen species. Ann Biomed Eng 39:674-87
Kalghatgi, Sameer; Kelly, Crystal M; Cerchar, Ekaterina et al. (2011) Effects of non-thermal plasma on mammalian cells. PLoS One 6:e16270