Farshid Guilak, Ph.D.- January 16, 2017

Engineering new biologic therapies for arthritis

Farshid Guilak, Ph.D.
Professor and Director
Center of Regenerative Medicine and Shriners Hospitals for Children – St. Louis
Departments of Orthopaedic Surgery, Developmental Biology, and Biomedical Engineering
Washington University, St. Louis MO

Osteoarthritis is a painful and debilitating disease of the joints that is characterized by progressive degeneration of the articular cartilage that lines the joint surfaces.  The etiology of osteoarthritis is poorly understood, although it is now well accepted that biomechanical factors play an important role in the onset and progression of this disease. The primary goal of our lab has been to determine the mechanisms by which mechanical loading affects the physiology of the joints.  Using a hierarchical approach to span different systems, ranging from clinical studies and in vivo animal models to studies at the tissue, cellular, and subcellular scale, we have identified specific mechanical signaling pathways that regulate cartilage physiology, pathology, and mechanically-induced regeneration. These pathways provide novel pharmacologic targets for the modification of cartilage degeneration in osteoarthritis.  Additionally, our studies have focused on stem-cell based approaches for repairing cartilage damage.  Using textile processes that allow weaving of biomaterial fibers in three dimensions, we have created cell-instructive bioactive scaffolds that can recreate many of the complex biomechanical properties and anatomic features of articular cartilage as a cell-based approach for complete resurfacing of osteoarthritic joint surfaces.  In recent years, the advent of synthetic biology and gene-editing methods such as CRISPR/Cas9 has allowed for precise modifying gene networks that control stem cell behavior. We have applied a combination of principles from these fields to rewire cellular gene circuits in a manner that allows us to create a unique, custom-designed cell type that can sense and respond to its biochemical environment in a pre-programmed way to developed engineered tissues with the ability for tunable, inducible, or feedback-controlled, auto-regulated biological responses.  In addition to recapitulating the biochemical and biomechanical properties of the tissue, these “smart” cells can provide controlled drug delivery and immunomodulatory responses to the joint to enhance the success of engineered tissue replacements.