Scientific Publications

Mesenchymal stromal cells (MSCs) may be of therapeutic value in the management of several hereditary, mechanical, and degenerative diseases like osteoarthritis (OA). Despite the fact that conservative treatment is successful in many patients with mild to moderate OA, a number of patients fail to respond and may not be suitable for surgery. Also, the current treatment strategies are not capable of preventing disease progression and hence cannot promise a pain-free life in the long term. A lot of research involving autologous as well as allogeneic MSCs is in progress in the field of regenerative medicine. This review comprehensively discusses the potential role of MSCs in treating OA.

Osteoarthritis (OA), one of the commonest chronic, inflammatory, and degenerative diseases, is known to affect synovial joints like the hip and knee. The inflammation and pain associated with this condition is usually treated in the clinic with anti-inflammatory drugs and analgesics. Patients with severe OA are compelled to opt for invasive knee replacement surgery eventually. The use of mesenchymal stromal cells (MSCs) in the treatment of OA has been extensively explored owing to their chondrogenic differentiation potential and anti-inflammatory properties. This chapter discusses the in vitro development of MSCs and findings of preclinical studies and clinical trials.

There is a growing body of evidence to show that mesenchymal stromal cells (MSCs) are a novel and promising option in the management of osteoarthritis (OA). This publication discusses various aspects of stem cell therapy, such as their sources, route of administration, dose of the cells, and therapeutic efficacy in OA. For knee OA, the ideal way of delivering the cells into the affected joint is by direct intraarticular injection of the MSCs into the knee synovium blindly or under ultrasound guidance. While the most efficacious dose to reduce inflammation and regenerate hyaline cartilage is being determined through clinical trials, the feasibility of repeating MSC injections for additional therapeutic benefit is also being studied.

This phase II trial explored the use of cell-based therapy to address repair of the damaged knee joint articular cartilage. In this study, the in vitro potential of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®) to differentiate into chondrocytes was determined. Sixty OA patients randomly received different doses of Stempeucel® (25, 50, 75, or 150 million cells injected intra-articularly) or placebo. The visual analog scale (VAS) for pain, intermittent and constant osteoarthritis pain (ICOAP), and Western Ontario and McMaster Universities Osteoarthritis (WOMAC-OA) index were used at baseline and at month 1, 3, 6, and 12 of follow-up for subjective evaluation. The cartilage was evaluated by magnetic resonance imaging of the knee, which was performed at baseline, and at 6- and 12-months follow-up. The study found that Stempeucel® differentiated into the chondrogenic lineage in vitro with down regulation of Sox9 and upregulation of Col2A genes. A significant reduction in pain and repair of the articular cartilage was observed in the preclinical study. In the clinical study, IA administration of Stempeucel® was found to be safe, and improvement was noted in the 25-million-cell dose group across all the subjective parameters.

The restoration of normal cartilage function in osteoarthritis (OA) has been difficult to achieve despite the availability of surgical and pharmaceutical interventions. Considering that the tissue primarily comprises chondrocytes in a specialized extracellular matrix bed, the bone marrow-derived 'mesenchymal stem cells' seem to be ideal for therapeutic use in cartilage regeneration, as their chondrogenic differentiation potential is inherent. Further, they can be easily isolated and cultured in an undifferentiated state for treatment purposes. As they have anti-inflammatory and immunosuppressive properties, allogeneic application is possible. The bioactive soluble factors secreted by them protect the cartilage from further damage and stimulate the remaining progenitor cells in situ to regenerate. This review discusses the advancements made in the last few years in using bone marrow-derived mesenchymal stem cells for repairing the damaged cartilage in OA.

Osteoarthritis is a chronic, progressive, and degenerative condition with limited therapy options. Recently, biologic therapies have been an evolving option for the management of osteoarthritis.