TY - JOUR
T1 - Genetic engineering of meniscal allografts
AU - Martinek, Vladimir
AU - Usas, Arvydas
AU - Pelinkovic, Dalip
AU - Robbins, Paul
AU - Fu, Freddie H.
AU - Huard, Johnny
PY - 2002
Y1 - 2002
N2 - Allograft meniscal transplantation represents one of the few available treatment options after menisectomy. Despite acceptable early results, a considerable controversy exists with regard to poor graft regeneration, shrinkage and biomechanical failure of transplanted menisci. Transfer of specific growth factor genes may improve the regeneration process of meniscal allografts. The aim of this study was to investigate the feasibility of gene transfer in meniscal allografts in rabbits. Four different viral vectors encoding marker genes, including lacZ, luciferase, and green fluorescence protein were used to investigate viral transduction in 50 lapine menisci for 4 weeks in vitro. Subsequently, 16 unilateral meniscus replacements were performed with ex vivo retrovirally transduced meniscal allografts, and the expression of the lacZ gene was examined histologically at 2, 4, 6, and 8 weeks after transplantation. Gene expression in the superficial cell layers of the menisci can be detected for up to 4 weeks in vitro, but the level of gene transfer declined over time. The transduction with retrovirus showed better persistence and deep penetration of the menisci with infected cells. In vivo, declining numbers of β-galactosidase-positive cells were also detected in retrovirally transduced allografts up to 8 weeks. Consistently, transduced cells were found at the menisco-synovial junction of the transplants and in deeper layers of the menisci. There was no evidence of cellular immune response in the transduced transplants. This investigation showed a prospective for growth factor delivery in auto- and allografts. In further experiments, vectors expressing therapeutic proteins such as growth factors will be investigated to assess their potential to improve remodeling and healing of meniscal allografts.
AB - Allograft meniscal transplantation represents one of the few available treatment options after menisectomy. Despite acceptable early results, a considerable controversy exists with regard to poor graft regeneration, shrinkage and biomechanical failure of transplanted menisci. Transfer of specific growth factor genes may improve the regeneration process of meniscal allografts. The aim of this study was to investigate the feasibility of gene transfer in meniscal allografts in rabbits. Four different viral vectors encoding marker genes, including lacZ, luciferase, and green fluorescence protein were used to investigate viral transduction in 50 lapine menisci for 4 weeks in vitro. Subsequently, 16 unilateral meniscus replacements were performed with ex vivo retrovirally transduced meniscal allografts, and the expression of the lacZ gene was examined histologically at 2, 4, 6, and 8 weeks after transplantation. Gene expression in the superficial cell layers of the menisci can be detected for up to 4 weeks in vitro, but the level of gene transfer declined over time. The transduction with retrovirus showed better persistence and deep penetration of the menisci with infected cells. In vivo, declining numbers of β-galactosidase-positive cells were also detected in retrovirally transduced allografts up to 8 weeks. Consistently, transduced cells were found at the menisco-synovial junction of the transplants and in deeper layers of the menisci. There was no evidence of cellular immune response in the transduced transplants. This investigation showed a prospective for growth factor delivery in auto- and allografts. In further experiments, vectors expressing therapeutic proteins such as growth factors will be investigated to assess their potential to improve remodeling and healing of meniscal allografts.
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U2 - 10.1089/107632702753503108
DO - 10.1089/107632702753503108
M3 - Article
C2 - 11886659
AN - SCOPUS:0036186320
SN - 1076-3279
VL - 8
SP - 107
EP - 117
JO - Tissue Engineering
JF - Tissue Engineering
IS - 1
ER -