EAPSI: Development of a Test-Tube Model for Studying Orthopedic Injuries Using Adult Stem Cells

Duncombe Todd A, Berkeley CA

Investigators

Abstract

The enthesis is the anatomical region where a tendon, ligament or joint capsule attaches to bone - and it plays a critical role in stress dissipation at tendon/bone interfaces. Inflammation of the enthesis, termed enthesitis, is most commonly caused by recurring physical stress or the autoimmune disorder, spondyloarthritis. In the United States, axial spondyloarthritis affects more than 2 million people a year. Despite the significant disease-burden, its pathology is poorly understood. This is in-part due to the lack of reliable methods for developing a model enthesis-organ outside of the body for testing. This research aims to investigate the optimal set of conditions to form a test-tube model of the enthesis-organ from a population of adult stem cells. This research will be conducted at National Taiwan University in collaboration with Professor Pen-hsiu Grace Chao, an expert in orthopedic injury and tissue engineering using mesenchymal stem cells. Results from this study could lead to clinically relevant strategies for both understanding enthesis damage and methods for repair. A microfluidic bioreactor will be developed to present chemical, electrical and mechanical cues to a homogenous population of mesenchymal stem cells to determine the optimal tissue engineering conditions to form an in vitro enthesis model. The spatial differentiation results - evaluated in-terms of cell morphology, alkaline phosphatase activity, glycosaminoglycan and calcium deposits in the extracellular matrix - will be used to directly assess the formation of the complex three-phase enthesis-organ (comprised of tendon, fibrocartilage and bone). Results from this study will inform strategies for creating an in vitro enthesis model and provide insights into novel joint-replacement procedures. This NSF EAPSI award is funded in collaboration with the National Science Council of Taiwan.