Project Title: Material-based modulation of cell binding

Project Duration: May 22 – July 28, 2017 (10 weeks), 40 hours per week.

Project Mentors –

• Primary Faculty Mentor (Name, Affiliation, website and Email/Phone):
  • Luke Mortensen, Department of Engineering/Animal and Dairy Science http://www.rbc.uga.edu/leaders/Mortensen.php, Luke.Mortensen@uga.edu, 706-542-0985

• Graduate Student/PostDoc mentors (Name, Affiliation and Email/Phone):
  • Emily Pendleton, Department of 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. Mesenchymal stem cells (MSC), cells that can differentiate into cartilage, fat and bone, have been used in the clinic for over a decade in the treatment of immune diseases and tissue repair. Yet, limited success of this treatment can likely be attributed to low engraftment of MSCs. Intravenously administered MSCs often become trapped in the lung and liver, with very few cells making it to the target organ. Thus a need to modify MSCs to increase cell homing to the site of tissue damage is needed. Several strategies have attempted to overcome this problem by engineering the cell surface to enhance binding at the target site. This summer’s project aims to use the opposite approach and reduce off-target binding using a material that modifies the adhesive properties of MSCs. Cell adhesion properties will be modified using a variety of polymer release agents. 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. Once the best modification of cell adhesion is determined, a murine model will be used to test MSC distribution and binding with evaluation done 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.