Cell-based resurfacing of large cartilage defects: long-term evaluation of grafts from autologous transgene-activated periosteal cells in a porcine model of osteoarthritis.
OBJECTIVE
To investigate the potential of transgene-activated periosteal cells for permanently resurfacing large partial-thickness cartilage defects.


METHODS
In miniature pigs, autologous periosteal cells stimulated ex vivo by bone morphogenetic protein 2 gene transfer, using liposomes or a combination of adeno-associated virus (AAV) and adenovirus (Ad) vectors, were applied on a bioresorbable scaffold to chondral lesions comprising the entire medial half of the patella. The resulting repair tissue was assessed, 6 and 26 weeks after transplantation, by histochemical and immunohistochemical methods. The biomechanical properties of the repair tissue were characterized by nanoindentation measurements. Implants of unstimulated cells and untreated lesions served as controls.


RESULTS
All grafts showed satisfactory integration into the preexisting cartilage. Six weeks after transplantation, AAV/Ad-stimulated periosteal cells had adopted a chondrocyte-like phenotype in all layers; the newly formed matrix was rich in proteoglycans and type II collagen, and its contact stiffness was close to that of healthy hyaline cartilage. Unstimulated periosteal cells and cells activated by liposomal gene transfer formed only fibrocartilaginous repair tissue with minor contact stiffness. However, within 6 months following transplantation, the AAV/Ad-stimulated cells in the superficial zone tended to dedifferentiate, as indicated by a switch from type II to type I collagen synthesis and reduced contact stiffness. In deeper zones, these cells retained their chondrocytic phenotype, coinciding with positive staining for type II collagen in the matrix.


CONCLUSIONS
Large partial-thickness cartilage defects can be resurfaced efficiently with hyaline-like cartilage formed by transgene-activated periosteal cells. The long-term stability of the cartilage seems to depend on physicobiochemical factors that are active only in deeper zones of the cartilaginous tissue.
Gelse
Kolja
K
University Hospital Erlangen, Erlangen, Germany.
Mühle
Christiane
C
Franke
Oliver
O
Park
Jung
J
Jehle
Marc
M
Durst
Karsten
K
Göken
Mathias
M
Hennig
Friedrich
F
von der Mark
Klaus
K
Schneider
Holm
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002357:Cartilage Diseases / Q000473:pathology / Q000628:therapy*; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D051457:Hyaline Cartilage / Q000473:pathology / Q000502:physiology; D008954:Models, Biological; D010003:Osteoarthritis / Q000473:pathology / Q000628:therapy*; D010521:Periosteum / Q000166:cytology*; D013552:Swine; D013556:Swine, Miniature; D016212:Transforming Growth Factor beta / Q000235:genetics; D019076:Transgenes; D014182:Transplantation, Autologous; D014945:Wound Healing
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta