A novel therapeutic combination of mesenchymal stem cells and stigmasterol to attenuate osteoarthritis in rodent model system— a proof of concept study

Mesenchymal stem cells (MSCs) have gained wide therapeutic acceptance in regenerative medicine due to their potential in repair process in restoring the damaged tissues and controlling inflammation. In the present study, we report for the first time the beneficial effects of combining placental-derived MSCs (hPMSCs) with stigmasterol-a plant-derived sterol to accelerate cartilage repair and regeneration in a monosodium-iodoacetate (MIA) induced osteoarthritis (OA) rat model. Control animals (Group I) received no treatment. Experimental animals (Group II) received a single intra-articular injection of MIA (2 mg) in the right knee joints. The Group II animals developed OA-like lesions within a week of MIA injection. They were subdivided further as: (II-A): OA, (II-B): OA+hPMSCs (2×106 cells, single-dose/intra-articular injection), (II-C): OA+stigmasterol (20 µg/mL, single-dose/intra-articular injection) and (II-D): OA+hPMSCs+stigmasterol. The animals were monitored for four more weeks after which they were sacrificed, the right limbs dissected out and assessed for cartilage repair and regeneration using micro-computed tomography (micro-CT) and histology. Results showed that the combined administration of hPMSCs with stigmasterol (II-D) was the most effective in correcting the OA lesions, with concomitant repair and regeneration. However, hPMSCs (II-B) or stigmasterol (II-C) per se treated groups showed only marginal beneficial effects and were not significant. Thus the present study provides valuable insights in situ using a combination of hPMSCs and stigmasterol towards cartilage repair and regeneration. We advocate the participation of populating cells or residual chondrocytes in addition to its anti-inflammatory functions.