Basic Science Research
Discovering novel treatments using a wide range of research techniques
From stem cell biology to genomics, the clinician scientists at the Department of Orthopaedic Surgery conduct scientific inquiries that pave the way to major breakthroughs in musculoskeletal treatments. Their multidisciplinary expertise extends far beyond surgical excellence to encompass biomechanics, immunology, physiology, pharmacology and more, ensuring that their laboratory discoveries translate into clinical applications.
Cartilage Regeneration and Stem Cell
Denis Evseenko, MD, PhD, bridges studies of early embryogenesis and stem cell biology to clinically relevant application of stem cell and small-molecule-based therapies. Current work addresses an unsolved question in the skeletal biology: What are the cellular and molecular components of the “niche” required for the long-term maintenance of cartilage-committed progenitors capable of differentiation into articular chondrocytes?
Recently, his research group defined the developmental progression through which primordial mesenchymal cells commit to the chondrocyte lineage in vivo. Based on these findings, the group now focuses on developing novel translational pluripotent stem cell and small-molecule-based approaches for articular cartilage and bone regeneration. His laboratory is actively using pre-clinical in vivo models of cartilage and bone injury and repair. (evseenkolab.usc.edu)
Bone Repair and Stem Cell/Gene Therapy
Jay R. Lieberman, MD, is a pioneer in the development of regional gene therapy to enhance bone repair. A number of difficult bone repair scenarios exist for which no consistently satisfactory solution is available, including: fracture nonunion, acute fractures with extensive bone loss, revision total joint arthroplasty and pseudarthrosis of the spine.
Traditionally, autologous bone graft has been the gold standard but, with a limited supply of this bone, concerns remain regarding the morbidity associated with graft harvest. Recombinant bone morphogenetic proteins (BMPs) are FDA-approved for use in spinal fusion and treatment of fresh tibial fractures. However, BMPs have had mixed success in humans and are associated with side effects including soft tissue edema and heterotopic ossification.
Orthopaedic surgeons have long sought alternative tissue engineering strategies to enhance bone repair. Lieberman aims to develop regional gene therapy using transduced bone marrow cells as a comprehensive tissue-engineering strategy to enhance bone repair. The Lieberman laboratory was the first to successfully heal a critical-sized femoral defect using bone marrow cells genetically manipulated to overexpress BMP.
Recently, his group developed a “same day” gene therapy strategy to facilitate clinical adaption of this regimen. Bone marrow cells were transduced with a lentiviral vector containing the cDNA for BMP-2 and successfully healed a large bone defect. The laboratory is now assessing the biologic potential of genetically manipulated human bone marrow cells and adipose-derived stem cells to move this strategy closer to the clinic.
Jeffrey Wang, MD, focuses on understanding the development of spinal disorders from both a clinical and basic science perspective. His laboratory has used a multidisciplinary approach to investigate the cause of degenerative spinal conditions and the efficacy of current treatments. This includes studying kinetic magnetic resonance imaging (kMRI) and insurance-billing-record databases (PearlDiver).
The main goal of the kMRI research is to further investigate degenerative changes that are only visible during spine loading and bending. Various clinical conditions, as well as changes in intervertebral discs, nerves and ligaments are studied in neutral, flexion and extension positions. The PearlDiver database analyses aim to characterize trends, costs and complications related to spinal treatments — both operative and conservative.
In vitro and in vivo studies constitute the Wang laboratory’s basic science approach and include projects on the development and prevention of spinal tumors, vertebral fusion and bone formation, and intervertebral disc tissue engineering. Close interactions within the Department of Orthopaedic Surgery, as well as with other research centers and spine societies, enable extensive collaboration on a range of projects.