Adult cells combined with platelet-rich plasma for tendon healing: Cell source options

Abstract

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 tenocyteconditioned 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.