A mixed co-culture of mesenchymal stem cells and transgenic chondrocytes in alginate hydrogel for cartilage tissue engineering

Abstract

To regenerate articular cartilage tissue from degeneration and trauma, synovial mesenchymal stem cells (SMSCs) were used in this study as therapeutic progenitor cells to induce therapeutic chondrogenesis. To accomplish this, chondrocytes pre-transduced with adenoviral vectors carrying the transforming growth factor (TGF) β3 gene were selected as transgenic companion cells and co-cultured side-by-side with SMSCs in a 3D environment to provide chondrogenic growth factors in situ. We adopted a mixed co-culture strategy for this purpose. Transgenic delivery of TGF-β3 in chondrocytes was performed via recombinant adenoviral vectors. The mixed co-culture of SMSCs and transgenic chondrocytes was produced in alginate gel constructs. Gene expression in both SMSCs and chondrocytes were characterized. Biochemical assays in vitro and in vivo showed that release of TGF-ß3 from transgenic chondrocytes not only induced SMSC differentiation into chondrocytic cells but also preserved the chondrocytic phenotype of chondrocytes from suspected dedifferentiation. As a result, this mixed co-culture strategy in conjunction with TGF-ß3 gene delivery could be a promising approach in cartilage tissue engineering.

Keywords: TGF-β3; adenoviral vector; chondrogenesis; gene delivery; mixed co-culture; synovial mesenchymal stem cells (SMSCs).