Advancing the health and well-being of animals and people


Fellow: Kira Novakofski
Mentor: Lisa Fortier

Department of Clinical Sciences
Email: kdn22@cornell.edu; Phone: 607-253-4453
Sponsor: Weill Cornell Medical College – NIH
Grant Number: TL1TR000459
Title: Cellular Biomarkers of Early Cartilage Injury Measured with Multiphoton Imaging
Project Amount: $27,232
Project Period: 07/01/13-06/30/14

DESCRIPTION (Provided by Applicant): The purpose of this study is to determine if traumatic injury of cartilage results in non-uniform spatial distribution of chondrocyte death and if this distribution is correlated to collagen fiber orientation in the transverse plane and can be imaged in vivo using multiphoton microscopy (MPM). In this proposal, articular cartilage will be traumatically compressed and resultant chondrocyte and matrix damage will be optically assessed in live tissue. If successful, this will be the first study to use a non-destructive live-imaging technique to define chondrocyte damage at the cellular level following impact injury. First, we will map damage in an ex vivo model to minimize experimental variables. Cartilage blocks will be harvested from horses. A single traumatic injury will be applied to the articular surface to model early posttraumatic osteoarthritis (PTOA). Cellular and structural injury will be optically assessed and quantified using MPM with angioscopic fluorescein dye and transmission electron microscopy. Data from MPM and collagen split line staining will be used to determine the dissemination of damage from the focal injury. Second, we will validate the use of MPM to detect early damage in an in vivo equine model of PTOA. Direct impact to an exposed cartilage surface will be applied in vivo and evaluated using an arthroscopic-adapted MPM lens. Replication of ex vivo methods to in vivo scenario is not always direct so there is a need to validate ex vivo findings to the in vivo situation. Use of an in vivo model is necessary to obtain long-term results and to evaluate potential therapeutics to prevent the development of PTOA. Our expectation is that the studies in this proposal will be translational to clinical use by future adaption of in vivo MPM for detecting early and/or subtle cartilage injury. Early detection of chondrocyte damage will allow for development and testing of therapeutics to stop the development of PTOA.