Transplantation of adenovirally transduced allogeneic chondrocytes into articular cartilage defects in vivo

Abstract

Gene transfer to chondrocytes followed by intra-articular transplantation may allow for functional modulation of chondrocyte biology and enhanced repair of damaged articular cartilage. We chose to examine the loss of chondrocytes transduced with a recombinant adenovirus containing the gene for Escherichia coli beta-galactosidase (Ad.RSVntlacZ), followed by transplantation into deep and shallow articular cartilage defects using New Zealand White rabbits as an animal model. A type I collagen matrix was used as a carrier for the growth of the transduced chondrocytes and to retain the cells within the surgically created articular defects. Histochemical analysis of matrices recovered from the animals 1, 3 and 10 days after implantation showed the continued loss of lacZ positive chondrocytes. The number of cells recovered from the matrices was also compared with the initial innoculum of transduced cells present within the matrices at the time of implantation. The greatest loss of transduced cells was observed in the first 24 h after implantation. The numbers of transduced cells present within the matrices were relatively constant between 1 and 3 days postimplantation, but had progressively declined by 10 days postimplantation. These results suggest that transduction of chondrocytes followed by intra-articular transplantation in this rabbit model may enable us to examine the biological effects of focal transgenic overexpression of proteins involved in cartilage homeostasis and repair.

Cartilage repair using bone morphogenetic protein 4 and muscle‐derived stem cells

“…During the cartilage healing process, 4 weeks of protein expression may be insufficient to generate mature repaired tissue. Our results, compared with those generated by MDC or chondrocyte transplantation (16,47,48), indicate that the better survival of transplanted MDSCs led to significantly enhanced and prolonged LacZ transgene expression within the cartilage lesions.…”

Gene-based approaches for the repair of articular cartilage

“…Similar results have been obtained with chondrocyte-seeded collagen type I matrices following genetic modification of the cells with adenovirus. 63,64 More recently it was found that transfected chondrocytes incorporated into alginate spheres and implanted into osteochondral defects in rabbit knees would express detectable levels of activity from marker genes from plasmid DNA for as long as 32 days. 45 Together, these studies confirm the feasibility of using chondrocytes as a means of ex vivo gene transfer to cartilage lesions and that prolonged expression of a transgene in vivo (ie X2 weeks) is feasible using commonly available vectors and three-dimensional supports.…”

Gene Therapy of Arthritis.

“…These cells are susceptible to adenoviral, and retroviral transduction, and ex vivo gene transfer to cartilage has been achieved with both of these vectors (44,45). Direct injection of adenoviral vectors into normal joints does not transduce chondrocytes, but neutral liposomes containing the hemaglutinizing virus of Japan can apparently diffuse into articular cartilage and deliver genes to chondrocytes in vivo (46).…”