Bone marrow mesenchymal stem cells overexpressing FGF-2 loaded onto a decellularized extracellular matrix hydrogel for the treatment of osteoarthritis

Abstract

Osteoarthritis, as one of the major disabling diseases in the elderly, has a long-term impact on patients’ quality of life and brings heavy medical and social burden. The pathogenesis of osteoarthritis is still unclear, and the main pathological changes include chondrocyte death and osteochondral damage. Therefore, how to solve the cartilage damage caused by osteoarthritis has become the key and difficult point in the clinical treatment of osteoarthritis. Bone marrow mesenchymal stem cells (MSCs) have the potential for self-renewal and multidirectional differentiation, and their engineering has been a hot research topic for the treatment of cartilage damage in recent years. In this study, an injectable hydrogel with stable and continuous release of growth factors was successfully prepared by modifying bone marrow mesenchymal stem cells to overexpress fibroblast growth factor-2 (FGF-2) and piggybacking on a decellularized extracellular matrix (dECM) hydrogel for the repair of cartilage injury in osteoarthritis. This hydrogel demonstrated excellent biocompatibility both in vitro and in vivo. In 3D cell culture, BMSCs in the dECM hydrogel survived, proliferated, and produced abundant cartilage-specific extracellular matrix and growth factors, promoting BMSC differentiation into hyaline chondrocytes. In vitro and in vivo experiments, along with RNA-seq analysis, showed that engineered BMSCs loaded onto the dECM hydrogel could inhibit chondrocyte apoptosis and boost BMSC differentiation. In summary, dECM hydrogels carrying FGF-2 overexpressing bone marrow mesenchymal stem cells have great prospects in accelerating osteochondral defect repair and delaying the progression of osteoarthritis.