Project Title: Material-based modulation of cell binding

Project Duration: May 25 – August 1, 2016 (10 weeks), 40 hours per week.

Project Mentors

• Primary Faculty Mentor (Name, Affiliation, website and Email/Phone): Luke Mortensen, Animal and Dairy Science Department/College of Engineering, http://www.rbc.uga.edu/leaders/Mortensen.php, mortensen@uga.edu, 706-542-0985
• Graduate Student/PostDoc mentors (Name, Affiliation and Email/Phone): Emily Pendleton, Interdisciplinary Neuroscience, pendleton25@uga.edu

Project Description: The promise of stem cell therapies to regenerate tissue has captured the imagination of the public and scientists alike. However, a number of recent clinical trials have failed- in part due to the challenge of controlling stem cell behavior after injection in the body. Bone marrow stem cells called mesenchymal stem cells (MSCs) differentiate to form cartilage, fat, and bone; and have been studied as a therapy with mixed success in bone diseases like osteoporosis or osteogenesis imperfecta. The majority of injected cells are trapped in the lungs and other organs, with only a small portion of the cells making it to the bone. Therefore, very low rates of MSC survival are observed and therapy is limited. Several strategies have attempted to overcome this problem by engineering the cell surface to enhance binding at the target site. This summer project will use the opposite approach and reduce off-target binding using a material that modifies the adhesive properties of MSCs. We will test a range of established polymer release agents for their effects on cell adhesion. We will then use these polymers as donors for nitric oxide, a powerful signaling molecule that regulates cell morphology and behavior. The effect of nitric oxide on cell viability and adhesive characteristics will be evaluated in vitro under static conditions and using a vascular mimic. The MSC distribution and binding in vivo will then be evaluated with high resolution in vivo multiphoton microscopy. Long term, engineering MSCs to selectively target    the bone and survive will enable treatment of debilitating bone diseases.

REU Student Role and Responsibility: During this research initiative, the REU student will first learn to culture and expand in vitro cells. The REU student will then evaluate viability and adhesion of cells with exposure to nitric oxide. The student will learn to form polymer formulations and evaluate their drug loading and release kinetics. MSC adhesion under static and flow conditions will be monitored, and if time permits in vivo homing will be evaluated using a multiphoton imaging platform. The student will learn a variety of skills and have the opportunity to work on an exciting project at the interface of materials and biology.

Expected Outcome for REU student: The proposed work is expected to advance a project focusing on the use of MSCs in bone regeneration, and will likely contribute to a future peer reviewed publication that will be targeted at a journal like Biomaterials or the Journal of Bone and Mineral Research. Results are anticipated to be presented at national and international meetings such as the Biomedical Engineering Society Annual Meeting and the American Society for Bone and Mineral Research.