Doherty P J, Zhang H, Tremblay L, Manolopoulos V, Marshall K W
Division of Rheumatology, Toronto Hospital Arthritis Centre, Toronto Hospital, Ontario, Canada.
Osteoarthritis Cartilage. 1998 May;6(3):153-9. doi: 10.1053/joca.1998.0107.
We are attempting to genetically-modify chondrocytes transplanted to cartilage in vitro as a prelude to gene therapy trials in patients with osteoarthritis.
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.
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.
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.
我们正尝试对体外移植到软骨的软骨细胞进行基因改造,以此作为骨关节炎患者基因治疗试验的前奏。
利用人类软骨和软骨细胞,我们探究了软骨细胞在体外与软骨结合的持续时间,以及在软骨细胞移植到软骨之前和之后,通过腺病毒载体感染导入软骨细胞的β-半乳糖苷酶基因的表达情况。
在我们最长的试验中,移植的软骨细胞在45天时仍继续与软骨外植体结合。在将软骨细胞移植到软骨至少35天后,我们能够成功地用腺病毒感染软骨细胞。β-半乳糖苷酶基因的表达在每个试验期间持续存在。
这些结果增加了通过用基因改造的软骨细胞覆盖软骨表面来修复和重建软骨的可能性。移植后能够很好地感染软骨细胞增加了反复感染表面软骨细胞的可能性,以此替代向关节腔反复注射软骨细胞。