Ovine synovial membrane-derived mesenchymal progenitor cells retain the phenotype of the original tissue that was exposed to in-vivo inflammation: evidence for a suppressed chondrogenic differentiation potential of the cells

The purpose of this study was to characterize the effect of post-surgery joint inflammation on the chondrogenic differentiation capacity of mesenchymal progenitor cells (MPCs) derived from the synovial membrane (SM). Six Suffolk-cross sheep were subjected to experimental anterior cruciate ligament (ACL) core surgeries. After they were killed 2 weeks after surgery, the volume of synovial fluid in the knees was measured and SM was collected for mRNA extraction and cell isolation. Cells were propagated and used for lineage-specific differentiation assays using cell pellet cultures and mRNA extraction. Chondrogenic differentiation assays in the presence of exogenous interleukin-1 beta (IL-1 beta) were also performed. The volume of synovial fluid from the operated knees was significantly greater than from the contralateral knees. Quantitative RT-PCR revealed that mRNA levels for IL-1 beta and matrix metalloproteinases-3 and -13 in SM from the operated knees were significantly higher than those from the contralateral knees. The size of MPC pellets from operated knees (opMPC) cultured in chondrogenic medium were significantly smaller than the corresponding pellets generated with MPCs from contralateral knees (conMPC). Addition of 1-100 ng/ml IL-1 beta significantly suppressed the resultant size of chondrogenic cell pellets from normal ovine SM-MPC. From these results, we conclude that cells from SM exposed to post-surgical inflammation are compromised by the inflammatory environment and that IL-1 beta can inhibit the latent chondrogenic potential of normal MPCs. This suggests that if MPCs from injured joints do contribute to cartilage repair, their endogenous repair potential may become compromised by such post-injury joint inflammation.