Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells

Abstract

Objective: To investigate the repair of partial-thickness lesions in rat articular cartilage by combining cell transplantation with transfer of growth factor complementary DNA (cDNA).

Methods: Mesenchymal cells isolated from rib perichondrium were infected ex vivo with adenoviral vectors carrying bone morphogenetic protein 2 (BMP-2) or insulin-like growth factor 1 (IGF-1) cDNA. The cells were suspended in fibrin glue and applied to mechanically induced partial-thickness cartilage lesions in the patellar groove of the rat femur. The filling of the defects was quantified and the quality and integration of the newly formed tissue were assessed by histochemical and immunohistochemical methods. Uninfected cells or cells infected with a LacZ reporter gene vector served as controls.

Results: Transplanted cells were able to attach to the wounded articular cartilage and were not displaced from the lesions by joint movement. Cells infected with both adenoviral vectors AdBMP-2 and AdIGF-1 produced repair cartilage of hyaline morphology containing a type II collagen-positive but type I collagen-negative proteoglycan-rich matrix that restored the articular surface in most lesions. Uninfected cells either failed to fill up the defects or formed fibrous tissue mainly composed of type I collagen. Excessive cells were partially dislocated to the joint margins, leading to osteophyte formation there if AdBMP-2-infected cells were used. These adverse effects, however, were not seen with AdIGF-1-infected cells.

Conclusion: Stimulation of perichondrium-derived mesenchymal cells by transfer of growth factor cDNA in a partial-thickness defect model allows for satisfactory cartilage restoration by a repair tissue comparable with hyaline articular cartilage.