Clinical application of mesenchymal stem cells for cartilage regeneration

Cartilage has the ability to transmit and distribute loads, providing lubrication in the diarthrodial joints. Risk factors including age, gender, genetics, nutrition and bone density may predispose to osteoarthritis (OA) and cartilage defect formation. Appropriate treatment include sufficient rest and medical therapy. Intra-articular injections such as steroids, platelet-rich plasma, visco-supplementation and mesenchymal stem cells (MSCs) injections present as alternative options for non-operative treatments. For cartilage defects, microfracture (MF), osteochondral autograft transplantation (OAT) and autologous chondrocyte implantation (ACI) are the most common treatment procedures. MSCs have been identified as an ideal cell source for OA therapy because they are easily expanded in culture, generally non-tumorigenic, and can be readily obtained from patients. It may be harvested from bone marrow (BMSCs), adipose tissue (ADSCs), synovium (SDSCs) or peripheral blood. BMSCs features the most common source of stem cells, and infrapatellar fat pad (IPFP) is another popular stem cell source. A phase 1 clinical study entitled “Treatment of Knee OA with Autologous Mesenchymal Stromal Cell Product (RegStem®)” was conducted in Taiwan and utilized 5 × 107 IPFP-MSCs in the study for OA therapy. Most of the existing clinical studies have shown that patients receiving MSCs treatment have improved clinical outcome, such as Visual Analogue Scale, International Knee Documentation Committee and Western Ontario and McMaster Universities Arthritis Index (WOMAC) score. Some studies have also found an improvement in cartilage volume by Magnetic Resonance Imaging evaluation. Furthermore, MSCs can also be used for cartilage defect treatment. Clinical outcomes such as IKDC, Lysholm, and Tegner scores showed significant improvement when the cartilage defects were repaired and regenerated by several millions of stem cells. A 10-year follow-up clinical research indicated that there was no apparent increased tumor formation risk when BMSCs were used for cartilage defect treatment. In addition, a BMSCs/collagen gel composite for cartilage repair clinical trial in Taiwan was conducted in 2008, and results suggested that there was an improvement in IKDC and MRI score at 9-years of follow-up. It appears that the use of MSCs for OA and cartilage defect treatment may be a promising method