Osteoarthritis (OA) is a disease of the synovial joint marked by chronic, low-grade inflammation leading to cartilage destruction. Regenerative medicine strategies for mitigating OA progression and/or promoting cartilage regeneration must be assessed using models that mimic the hallmarks of OA. More specifically, these models should maintain synovial macrophage phenotype in their native micro-environment. Herein, an in vitro coculture model of patient-matched human OA cartilage and synovium was assessed for viability, macrophage phenotype, and progressive cartilage destruction in the presence of an inflammatory milieu. Additionally, the influence of synovial macrophages and their polarization within the model was defined using depletion studies. Finally, the model was used to compare the ability of human amniotic stem cells (hAMSCs) and human adipose stem cells (hADSCs) to mitigate OA progression. OA cocultures demonstrated progressive and significant reductions in chondrocyte viability and cartilage glycosaminoglycan content within a proinflammatory environment. Selective depletion of synovial macrophages resulted in significant decreases in M1:M2 percentage ratio yielding significant reductions in concentrations of interleukin-1 beta, matrix metalloproteinase-13 and attenuation of cartilage damage. Finally, hAMSCs were found to be more chondroprotective versus hADSCs as indicated by significantly improved OA chondrocyte viability (89.8 ± 2.4% vs. 58.4 ± 2.4%) and cartilage glycosaminoglycan content (499.0 ± 101.9 μg/mg dry weight vs. 155.0 ± 26.3 μg/mg dry weight) and were more effective at shifting OA synovial macrophage M1:M2 ratio (1.3:1 vs. 5:1), respectively. Taken together, the coculture model mimics salient features of OA, including macrophage-mediated cartilage destruction that was effectively abrogated by hAMSCs but not hADSCs.

Osteoarthritis (OA) is a progressive degenerative disease that manifests as pain and inflammation and often results in total joint replacement. There is significant interest in understanding how intra-articular injections made from autologous blood or bone marrow could alleviate symptoms and potentially intervene in the progression of the disease. There is in vitro an in vivo evidence that suggests that these therapies, including platelet-rich plasma (PRP), autologous anti-inflammatories (AAIs), and concentrated bone marrow aspirate (cBMA), can interrupt cartilage matrix degradation driven by pro-inflammatory cytokines. This review analyzes the evidence for and against inclusion of white blood cells, the potential role of platelets, and the less studied potential role of blood plasma when combining these components to create an autologous point-of-care therapy to treat OA. There has been significant focus on the differences between the various autologous therapies. However, evidence suggests that there may be more in common between groups and perhaps we should be thinking of these therapies on a spectrum of the same technology, each providing significant levels of anti-inflammatory cytokines that can be antagonists against the inflammatory cytokines driving OA symptoms and progression. While clinical data have demonstrated symptom alleviation, more studies will need to be conducted to determine whether these preclinical disease-modifying findings translate into clinical practice.