| dc.description.abstract | After decades of research, the therapeutic mechanism of mesenchymal stem cells (MSC) remains unknown. While most agree that paracrine function is likely, little is known about the influence of cellular or tissue contact. Our objective was to develop a model of synovitis of the equine articular joint to further understand the role of cell-to-cell contact on MSC function. We tested four conditions (co-culture, transwell, conditioned media and co-culture with a cartilage explant) and found that contact with synovial cells (SCs) and chondrocytes in the presence of interleukin 1-beta (IL1-β) significantly altered cellular secretions. We then added synovial fluid to the cartilage co-culture model to examine the effects on MSCs and dermal fibroblasts (DFs). Compared to DFs, MSCs induced increased prostaglandin E2 (PGE2) in all conditions of contact, increased interleukin-6 (IL-6), decreased interleukin-10 (IL-10) and increased growth-related oncogene (GRO) in conditions of co-culture with and without a cartilage explant. The addition of synovial fluid to the cartilage co-culture had little effect on cytokine production, but resulted in SC death, mediated by an anti-bovine serum albumin (BSA) antibody. While soluble factors contribute to communication between SCs, MSCs, and chondrocytes, direct contact with MSCs altered the cellular function and secretome of SCs and MSCs. This work suggests that cross-talk in combination with cell-to-cell contact between MSCs, synovial cells and chondrocytes is important for MSC immunomodulation. While there is still much to discover about the MSC secretome and how paracrine signaling contributes to MSC function in tissue repair, this work sheds light on the complexity of cell-to-cell communication in the joint environment. | |
