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. CONCLUSION: 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.

Restricted-expressed proliferation-associated protein (Repp86) expression in squamous cell carcinoma of the oral cavity.

PURPOSE: To determine the expression of repp86 (restricted-expressed protein of 86 kDa theoretical molecular mass), a proliferation- associated protein expressed in S-, G(2)- and M-phases of the cell cycle, in samples of normal mucosa as well as squamous cell carcinoma of the oral cavity (OSCC). PATIENTS AND METHODS: The repp86 labeling index (LI) was determined imunohistochemically in ten samples of normal oral mucosa and 59 samples of OSCC. Repp86 LI was correlated with tumor stage, histopathologic grading, and the expression of Ki-67 and topoisomerase IIalpha. RESULTS: Repp86 was detectable in all tissues analyzed. The mean LI was 4.7% for normal mucosa and 18.4% for squamous cell carcinoma (p < 0.0001). Repp86 expression was not related to tumor size, lymph node invasion, or histopathologic grading but was positively correlated with Ki-67 index (r = 0.48; p < 0.01) as well as with topoisomerase IIalpha (r = 0.39; p < 0.01). Ki-67 and topoisomerase IIalpha levels were also significantly correlated with each other (r = 0.34; p < 0.05). CONCLUSION: These results indicate that repp86 expression can be an additional proliferation marker among Ki-67 and topoisomerase IIalpha in OSCC. Further research will be directed at the evaluation of the prognostic value of repp86 expression in OSCC as well as in leukoplakia and early-stage OSCC.