Abstract
Recently, therapy with bone marrow mesenchymal stem cells (BMMSCs) has been attempted to relieve rheumatoid arthritis (RA) and reconstruct cartilage injury. However, treatment has been unsuccessful in complete prevention of persistent cartilage destruction and resulted in inferior outcomes of cartilage regeneration. Scaffolds are an important construct in the field of cartilage tissue engineering, but their role in arthritis treatment has not yet been fully examined. Here, we transplanted two types of scaffold-assisted BMMSCs: fibrin gel- and poly(l-lactide-co-glycolide)−poly(ethylene glycol)−poly(l-lactide-co-glycolide) (PLGA−PEG−PLGA) hydrogel-assisted BMMSCs referred as FGB and HGB groups, respectively, into subchondral defects for the treatment of antigen-induced arthritis. The administration of exogenous BMMSCs ameliorated joint swelling and decreased both joint surface temperature and inflammatory cytokine levels in both groups. Immune cell composition of the inflammation of surrounding synovium, protection of adjacent cartilage, and improved cartilage repair were also observed. Overall, the HGB group had a better therapeutic efficacy than the FGB group. In conclusion, local transplantation of BMMSCs in subchondral defects presents a novel approach in inducing RA remission and recovery of RA-induced cartilage injury. To induce these changes, the selection of scaffold for cell support is exceedingly important. Further studies are needed regarding the treatment options of subchondral defects in arthritis based on modified scaffold development, application of defined MSCs sources, combination of pharmacotherapeutics, and the addition of factors that inhibit the processes of RA remission, promote the recovery of RA-induced cartilage injury and the relationship between these factors.
Highlights
Rheumatoid arthritis (RA) leads to persistent cartilage destruction due to chronic inflammation and intractable synovial hyperplasia
The administration of bone marrow mesenchymal stem cells (BMMSCs) contributed to the immune regulation of inflammation of the tissue surrounding the synovium, the protection of the tissue adjacent to the cartilage and the improved cartilage repair
The administration of exogenous BMMSCs ameliorated the symptoms of joint swelling and elevation of joint surface temperature and resulted in the decreased levels of inflammatory cytokines
Summary
Rheumatoid arthritis (RA) leads to persistent cartilage destruction due to chronic inflammation and intractable synovial hyperplasia. Mesenchymal stem cells (MSCs) are used in regenerative medicine primarily because of their capacity to differentiate into specific cell types of mesenchymal origin, such as chondrocytes, osteoblasts and adipocytes [2] They can have an important role by secreting soluble factors that promote tissue regeneration [3]. It can respond to a minute change in environmental conditions with a large change in physicochemical properties, degradation, sol-gel phase transition and shape transformation Those properties make hydrogels widely applied in the fields of tissue engineering and controlled drug delivery [21,22]. We proposed a hypothesis that if different constituent scaffolds-assisted BMMSCs were transplanted in subchondral defects in an antigen-induced rabbit model (Figure 1), they may exert inconsistent functions on local immunosuppression, preventing cartilage damage as well as repairing cartilage defects under inflammatory conditions.
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