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Introduction: Osteoarthritis affects the whole joint and is usually treated using pain relief for many years followed by arthroplasty. Mesenchymal stem/stromal cells have the potential to form cartilage and bone and have been investigated for their capacity to repair these tissues, but until recently there has been no strong rationale for their use in the treatment of age-related, idiopathic osteoarthritis. Objectives: The aim of this review is to explore the origins of cell therapy for joint diseases and how the early work in cartilage repair has built toward the possibility of an injectable mesenchymal cell approach for osteoarthritis. Methods: A broad selection of publications has been identified relating to cartilage repair, mesenchymal cell biology, meniscal cartilage repair, and osteoarthritis therapeutics. Primary studies as well as several systematic reviews and meta-analyses have been included. Results: Cell therapies for cartilage lesions have been shown to be successful for traumatic injury but will be difficult to adapt for the treatment of idiopathic osteoarthritis. However the biological understanding of mesenchymal cells as a reservoir for trophic factors has led to their use as an injectable therapy. These studies have provided good evidence that sustained pain reduction can be achieved by injecting mesenchymal cells into the osteoarthritic joint, with some evidence also for functional improvement. Exosomes derived from mesenchymal may provide a scalable alternative to the cell therapy approach in future. Conclusions: Mesenchymal cells have potential as a possible injectable cell therapy for idiopathic osteoarthritis and should be further explored through larger-scale, carefully designed clinical trials.

To determine whether it is possible to engineer 3‐dimensional hyaline cartilage using mesenchymal stem cells derived from the bone marrow (BMSCs) of patients with osteoarthritis (OA).Expanded BMSCs derived from patients with hip OA were seeded onto polyglycolic acid scaffolds and differentiated using transforming growth factor β3 in the presence or absence of parathyroid hormone–related protein (PTHrP) to regulate hypertrophy. Micromass pellet cultures were established using the same cells for comparison. At the end of culture, the constructs or pellets were processed for messenger RNA (mRNA) analysis by quantitative real‐time reverse transcription–polymerase chain reaction. Matrix proteins were analyzed using specific assays.Cartilage constructs engineered from BMSCs were at least 5 times the weight of equivalent pellet cultures. Histologic, mRNA, and biochemical analyses of the constructs showed extensive synthesis of proteoglycan and type II collagen but only low levels of type I collagen. The protein content was almost identical to that of cartilage engineered from bovine nasal chondrocytes. Analysis of type X collagen mRNA revealed a high level of mRNA in chondrogenic constructs compared with that in undifferentiated BMSCs, indicating an increased risk of hypertrophy in the tissue‐engineered cells. However, the inclusion of PTHrP at a dose of 1 μM or 10 μM during the culture period resulted in significant suppression of type X collagen mRNA expression and a significant decrease in alkaline phosphatase activity, without any loss of the cartilage‐specific matrix proteins.Three‐dimensional hyaline cartilage can be engineered using BMSCs from patients with OA. This method could thus be used for the repair of cartilage lesions. [ABSTRACT FROM AUTHOR]

To assess the associations between pain, loss of function, and radiographic changes in knee osteoarthritis (OA), taking into account both the patellofemoral and tibiofemoral compartments. Both knees of 167 community‐based patients with OA in at least 1 of their knees were assessed. Pain was measured by visual analog scale, and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index. Anteroposterior standing radiographs with the knee in extension and lateral 30° flexion were obtained and assessed for the Kellgren/Lawrence score and for individual features (osteophytes, joint space narrowing, and subchondral bone sclerosis) in each compartment.Knees with structural changes in both compartments were more likely to be painful and to be associated with loss of function than were knees in which only 1 compartment was affected. The individual feature most strongly associated with pain was subchondral bone sclerosis.Studies exploring the associations between structural and symptomatic knee OA need to include an assessment of the patellofemoral compartment, and individual radiographic features rather than a global severity score should be considered in these studies. [ABSTRACT FROM AUTHOR]