J. Bolander (Winston Salem, US)
Wake Forest Institute for Regenerative Medicine Wake Forest Institute for Regenerative MedicinePresenter Of 1 Presentation
18.3.5 - The Synovial Environment Steers Cartilage Deterioration and Regeneration
Abstract
Purpose
Osteoarthritis (OA) is initiated by trauma in the joint that fails to heal. The trauma leads to activation of immune cells that orchestrates neighboring progenitor cells to migrate to the injured site where they attach, proliferate and undergo differentiation for regeneration to occur. It is currently not understood why this process fails upon chondral injury in the synovial joint.
Methods and Materials
Synovial fluid(SF) collected from patients diagnosed with early OA was processed to separate cells and SF. Cells were assessed for attachment, proliferation, migration and chondrogenic differentiation in the presence/absence of SF. Characterization of the SF led to the development of an immunomodulatory cell-treatment based on cartilage activated T-cells and progenitor cells. The cell treatment was evaluated by intra-articular injection in a rat model of Monosodium Iodoacetate-(MIA) induced OA. OA progression and resolution was evaluated by histology and IHC three weeks post cell-injection. In a final step the autologus treatment was evaluated in a compassionate use clinical study.
Results
SF-derived progenitor cells were able to attach, migrate, proliferate and undergo chondrogenic differentiation under standard conditions.
These abilities were impaired (p<0.05) in the presence of 10% SF, figure 1. Characterization of the SF confirmed de-differentiation of healthy articular chondrocytes as well as activation of pro-inflammatory events including neutrophil migration and elastase activity together with lymphocyte proliferation. Intraarticular injection of the pro-regenerative cell treatment in a rat OA-model led to articular cartilage regeneration confirmed by a matrix rich in glycosaminoglycans, collagen type 2 and Lubricin, figure 2.
The treatment led to an improved OARSI score for matrix degradation of 0 (p<0.05), from 4 in the non-treated control. In a clinical study for compassionate use, the immunomodulatory treatment restored deteriorated articular cartilage upon trauma-induced OA.
Conclusion
These findings confirm the crucial role of a balanced immune environment as a way to regenerate hyaline articular cartilage while treating degenerative joint disease.