Comparative Chondrogenic Potential of Equine Fetal Progenitor Cells and Adult Mesenchymal Stem Cells

Degenerative joint disease (DJD), or osteoarthritis, is a major cause of lameness and loss of athletic performance in horses. Osteoarthritis is also a significant source of morbidity in humans and dogs. New cell-based strategies to repair joint surface lesions are generating a high level of interest, but have yet to achieve full restoration of articular cartilage structure and function. Interzone cells are synovial joint progenitor cells that exist in mammals only during a short developmental window in the fetus. Our longterm goal is to identify cells that differentiate into true articular chondrocytes and can generate normal articular cartilage. The hypothesis to be tested in this project is that interzone cells have chondrogenic potential that exceeds that of adult mesenchymal stem cells. To test this hypothesis we propose to compare the histological features and expression of key chondrocyte biomarker genes in different fetal (interzone, cartilage anlagen chondrocytes, dermal fibroblasts) and adult (bone marrow mesenchymal stem cells (MSC), adipose MSC, articular chondrocytes, dermal fibroblast) cell lines under chondrogenic induction conditions. Histological assessment will include cell morphology and matrix components determined by special stains. Total RNA will be isolated and the expression of three key chondrocyte marker genes (COL1A1, COL2A1, ACAN) will be determined using quantitative PCR. The results from this study will be published and used as preliminary data to pursue funding for transcriptome level analyses (gene locus and transcript isoforms) comparing differences between mesenchymal stem cells under chondrogenic conditions and articular cartilage. Additionally, the proposed study will advance our understanding of the interzone, a novel and promising developmental tissue in cell-based regenerative therapies for articular lesions.