Objective: Arthritic synovial fluid (SF) contains mesenchymal stem cells (MSCs), which could simply reflect their shedding from diseased joint structures. This study used the bovine model to explore SF MSCs in health and enumerated them at the earliest stages of human osteoarthritis (OA) in radiographically normal joints.Methods: Clonogenicity and multipotentiality of normal bovine SF MSCs were compared with donor‐matched bone marrow (BM) MSCs at the single‐cell level. The colony‐forming unit–fibroblastic assay was used for MSC enumeration. The XTT assay was employed to assess cell proliferation, and flow cytometry was used to investigate the marker phenotype of bovine and human SF MSCs.Results: Single MSCs were present in normal bovine SF, and 96% of them were able to expand at least 1 million–fold. These cells were CD271–, multipotential, considerably more clonogenic, and less adipogenic than matched BM MSCs. In both pellet assays and on polyglycolic acid scaffolds, SF clones displayed consistent chondrogenic differentiation, while BM clones were variable. MSCs were present in arthroscopically normal human joints and were increased 7‐fold in early OA (P = 0.034). Their numbers correlated with numbers of free microscopic synovial tissue fragments (r = 0.826, P < 0.0001). OA SF had a growth‐promoting effect on synovial MSCs.Conclusion: This study confirms the presence of MSCs in normal SF and shows their numerical increase in early human OA. SF MSCs are likely to originate from synovium. These findings provide a platform for the exploration of the potential role of SF MSCs in joint homeostasis and for investigation of their utility in novel joint regeneration strategies.
1 November 2014 in International Journal of Pharmaceutics
Infection is the major reason for GTR/GBR membrane failure in clinical applications. In this work, we developed GTR/GBR membranes with localized drug delivery function to prevent infection. Hierarchical membranes containing micro- and nano-fibers were fabricated. The effects of the incorporation of gelatin and loading content of metronidazole (MNA) (0, 5, 10, 20, 30, and 40 wt% polymer) on the properties of the electrospun membranes were investigated. The interaction between PCL and MNA was identified by molecular dynamics simulation. MNA was released in a controlled manner, and the antibacterial activity of the released MNA remained. The incorporation of gelatin and MNA improved the hydrophilicity, biocompatibility, and in vitro biodegradation rate of PCL nanofibers. The electrospun membranes allowed cells to adhere to and proliferate on them and showed excellent barrier function. The membrane loaded with 30% MNA had the best comprehensive properties. Subcutaneous implantation results demonstrated that MNA-loaded membranes evoked a less severe inflammatory response than pure PCL nanofibers. These results demonstrated the potential of MNA-loaded membranes as GTR/GBR membranes with antibacterial and anti-inflammatory functions for biomedical applications.
1 March 2008 in Journal of Tissue Engineering and Regenerative Medicine