Adult Cells Combined With Platelet-Rich Plasma for Tendon Healing: Cell Source Options

BACKGROUND: The combination of cells with platelet-rich plasma (PRP) may fulfill tendon deficits and help overcome the limited ability of tendons to heal. PURPOSE: To examine the suitability of 3 human cell types in combination with PRP and the potential impact of the tenocyte-conditioned media (CM) to enhance tendon healing. STUDY DESIGN: Controlled laboratory study. METHODS: Tenocytes, bone marrow–derived mesenchymal stem cells, and skin fibroblasts were cultured in 3-dimensional PRP hydrogels supplemented or not with CM, and cell proliferation and migration were examined. The effect of tendon-derived CM on matrix-forming phenotype and secretion of inflammatory proteins was determined through their administration to mesenchymal stem cells, tendon, and skin fibroblasts by reverse transcription quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Differences were found in the matrix-forming phenotype between each of the cell types. The ratio of collagen I:collagen III was greater in bone marrow–derived mesenchymal stem cells than in skin fibroblasts and tenocytes. The bone marrow–derived mesenchymal stem cells expressed increased levels of cartilage-related genes than tenocytes or skin fibroblasts. The presence of the tenocyte-CM stimulated basic healing mechanisms including proliferation and chemotaxis in all cell types. In addition, the tenocyte-CM modified the matrix-forming phenotype of every cell type when cultured in PRP hydrogels. Each cell type secreted interleukin-6, interleukin-8, and monocyte chemotactic protein-1 in PRP hydrogels, but mesenchymal stem cells secreted less interleukin-8 and monocyte chemotactic protein-1 than tenocytes or skin fibroblasts. CONCLUSION: The tenocyte-CM combined with PRP stimulated tenogenesis in mesenchymal stem cells and in skin fibroblasts and reduced the secretion of inflammatory proteins. CLINICAL RELEVANCE: Modifying the target tissue with PRP prior to cell implantation may optimize the effect of cell therapies. Skin fibroblasts and bone marrow–derived mesenchymal stem cells combined with PRP could be used to regenerate tendons.