Factors affecting the efficacy of bovine chondrocyte transplantation in vitro.
Current therapies for osteoarthritis have been primarily directed at symptom relief rather than disease modification or cure. Improved understanding of cartilage biology and metabolism has permitted exploration of disease-modifying treatments for OA. Chondrocyte transplantation is one approach to disease modification that has received increasing attention. To date, most chondrocyte transplantation has focused on surgical implantation into isolated chondral defects.Our hypothesis is that cultured chondrocytes will preferentially transplant to hyaline cartilage after intraarticular injection. The purpose of this study was to quantify chondrocyte adherence to cartilage in an in-vitro bovine explant model under differing culture conditions. The effect on chondrocyte transplantation of time, of alginate vs. monolayer culture techniques, and of differing origin of tissue explants within the knee joint were assessed. The effect on transplantation of physically modifying the explant surface was also assessed. In addition to quantification of transplantation adherence, the morphology of transplanted chondrocytes was assessed with confocal and electron microscopy. Maximal adherence occurred by 24 h post-transplantation. Baseline transplant densities exceeding 1 x 10(6) cells/cm(2)were observed on unmodified cartilage surfaces. No significant differences in binding density were noted between cartilage explants obtained from the patella, femoral condyles, tibial plateaus or the trochlear groove. In addition, no differences in chondrocyte adherence were noted in cells cultured in monolayer or alginate beads. Transplanted chondrocytes were noted to be spherical irrespective of the culture methods employed. Notably, chondrocytes demonstrated significantly improved adherence to cartilage surfaces after the superficial layer was removed as compared to normal intact cartilage surfaces (increase of 26%, P< 0. 01). This suggests that chondrocytes may preferentially adhere to cartilage surfaces where the superficial layer has been damaged, as is the case in isolated chondral lesions, or with diffuse cartilage degeneration.
Manolopoulos
V
V
Division of Rheumatology, Toronto Hospital Arthritis Centre, McLaughlin13-406, 399 Bathurst Street, Toronto, Ontario, M5T 2S8.
Marshall
K W
KW
Zhang
H
H
Trogadis
J
J
Tremblay
L
L
Doherty
P J
PJ
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D002417:Cattle; D002448:Cell Adhesion; D002452:Cell Count; D019902:Chondrocytes / Q000502:physiology / Q000637:transplantation* / Q000648:ultrastructure; D003094:Collagen / Q000378:metabolism; D046508:Culture Techniques; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning
D003094:Collagen