Transplantation of adenovirally transduced allogeneic chondrocytes into articular cartilage defects in vivo.
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.
Baragi
V M
VM
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
Renkiewicz
R R
RR
Qiu
L
L
Brammer
D
D
Riley
J M
JM
Sigler
R E
RE
Frenkel
S R
SR
Amin
A
A
Abramson
S B
SB
Roessler
B J
BJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002358:Cartilage, Articular / Q000293:injuries*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000637:transplantation*; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D011817:Rabbits; D014162:Transfection