An in vitro model for osteoarthritis using long-cultured inflammatory human macrophages repeatedly stimulated with TLR agonists.

Osteoarthritis (OA) is characterized by an abundance of inflammatory M1-like macrophages damaging local tissues. The search for new potential drugs for OA suffers from the lack of appropriate methods of long-lasting inflammation. Here we developed and characterized an in vitro protocol of long-lasting culture of primary human monocyte-derived macrophages differentiated with a combination of M-CSF+GM-CSF that optimally supported long-cultured macrophages (LC-Mϕs) for up to 15 days, unlike their single use. Macrophages repeatedly stimulated for 15 days with the TLR2 ligand Pam3CSK4 (LCS-Mϕs), showed sustained levels over time of IL-6, CCL2, and CXCL8, inflammatory mediators that were also detected in the synovial fluids of OA patients. Furthermore, macrophages isolated from the synovia of two OA patients showed an expression profile of inflammation-related genes similar to that of LCS-Mϕs, validating our protocol as a model of chronically activated inflammatory macrophages. Next, to confirm that these LCS-Mϕs could be modulated by anti-inflammatory compounds, we employed dexamethasone and/or celecoxib, two drugs widely used in OA treatment, that significantly inhibited the production of inflammatory mediators. This easy-to-use in vitro protocol of long-lasting inflammation with primary human macrophages could be useful for the screening of new compounds to improve the therapy of inflammatory disorders.

Placenta-Derived Products Demonstrate Good Safety Profile and Overall Satisfactory Outcomes for Treating Knee Osteoarthritis: A Systematic Review of Clinical Evidence.

PURPOSE: To summarize the available evidence regarding the clinical application of placenta-derived products to treat knee osteoarthritis (OA), underlining the differences existing among products, their preparation methods, and the clinical results reported so far. METHODS: A research on PubMed, Cochrane, and Google Scholar databases was performed. The following inclusion criteria for relevant articles were used: (1) randomized controlled trials (RCTs), prospective and retrospective studies, on humans; (2) written in English; (3) published in indexed journals in the last 10 years (2011-2022); and (4) dealing with the use of placenta-derived products for the treatment of knee OA. Exclusion criteria were articles written in other languages; animals or in vitro trials; reviews; and trials analyzing other applications of placenta-derived products not related to knee OA. RESULTS: In total, 16 studies were included in the present systematic review. Five studies investigated placenta-derived products as an augmentation during surgical procedures, whereas 11 studies were focused on the injective approach only. Of these, only 4 were RCTs and were all from the injective approach group. Potential risk of bias was carried out using Cochrane Risk of Bias 2 tool for RCTs and a modified Coleman approach for nonrandomized studies, revealing for both an overall insufficient quality. Clinical outcomes reveal excellent safety profile and notable efficacy, despite the different types of products used and different administration methods adopted. CONCLUSIONS: Placental products showed a good safety profile and overall satisfactory outcomes for the treatment of knee OA. LEVEL OF EVIDENCE: Level IV, systematic review of Level II, III and IV studies.