Resurfacing of articular cartilage explants with genetically-modified human chondrocytes in vitro.
OBJECTIVE
We are attempting to genetically-modify chondrocytes transplanted to cartilage in vitro as a prelude to gene therapy trials in patients with osteoarthritis.


METHODS
With human cartilage and chondrocytes, we have explored the duration of binding of chondrocytes to cartilage in vitro and the expression of the beta-galactosidase gene introduced into the chondrocytes through infection with an adenoviral vector both before and after transplant of the chondrocytes to cartilage.


RESULTS
Transplanted chondrocytes continued to bind to cartilage explants at 45 days in our longest trial. We could successfully infect chondrocytes with adenovirus at least 35 days after we transplanted the chondrocytes to cartilage. Expression of the beta-galactosidase gene continued throughout the duration of each trial.


CONCLUSIONS
These results raise the possibility of repairing and rebuilding cartilage by resurfacing the cartilage with genetically modified chondrocytes. The ability to infect chondrocytes well after transplant raises the possibility of repeated infections of surface chondrocytes as an alternative to repeated injections of chondrocytes into the joint space.
Division of Rheumatology, Toronto Hospital Arthritis Centre, Toronto Hospital, Ontario, Canada.
P J
PJ
Doherty
H
H
Zhang
L
L
Tremblay
V
V
Manolopoulos
K W
KW
Marshall
D000256:Adenoviridae; D002358:Cartilage, Articular / Q000166:cytology*; D002448:Cell Adhesion; D019902:Chondrocytes / Q000637:transplantation*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D009924:Organ Culture Techniques; D010003:Osteoarthritis / Q000628:therapy*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D001616:beta-Galactosidase