Engineering osteogenesis and chondrogenesis with gene-enhanced therapeutic cells

For bone and cartilage regeneration, a direct dose of growth factors or the viral or non-viral vector-mediated delivery of growth factor genes to the site of osteal or chondral wounds has disadvantages. These limitations include the short half-life and instability of the proteins, resulting in low efficacy with the repeated administration of the therapy, and the nonspecific targeting of the therapy that elevates general toxicity and systemic immunogenicity. To address these challenges, the focus of gene therapy for bone and cartilage repair has shifted in recent years to the use of autologous cells, typically osteocytes or chondrocytes, or their progenitors, transfected with therapeutic genes; the cells are cultivated in vitro before in vivo transplantation. These gene-enhanced therapeutic cells provide sustained autocrine/paracrine stimulation and localized gene expression. An important advantage of the cell-based approach is that factors contributing to off-target toxicity and immunogenicity are metabolically cleared during the in vitro incubation of the transfected cells prior to being administered to the transplant recipients. This review focuses on gene therapy approaches for treating bone and joint disorders, and specifically discusses the development of cell-based delivery approaches.