Menisci are Efficiently Transduced by Recombinant Adeno-Associated virus Vectors in Vitro and in Vivo

Abstract

Background

Meniscal tears remain an unsolved problem in sports medicine. Gene transfer is a potential approach to enhancing meniscal repair. Recombinant adeno-associated virus is a method of gene transfer that has advantages over previously used approaches to this problem.

Hypothesis

Direct gene transfer to meniscal cells can be accomplished using recombinant adeno-associated virus in vitro and in vivo.

Study Design

Controlled laboratory study.

Methods

Recombinant adeno-associated viruses containing the reporter gene lacZ were tested for their ability to achieve gene transfer into lapine and human meniscal cells in vitro and into lapine meniscal defects in vivo. Results were assessed by detecting β-galactosidase, the enzyme encoded by the lacZ gene.

Results

Maximal efficiency of gene transfer was 81.6% ± 6.6% for lapine and 87.2% ± 14.8% for human meniscal cells in vitro. Expression of the transferred gene continued for the 28-day duration of the study. When the recombinant adeno-associated virus vector was injected into meniscal tears in a lapine meniscal tear model, transgene expression continued in meniscal cells adjacent to the tear for at least 20 days in vivo.

Conclusions

The data suggest that recombinant adeno-associated virus vectors can directly and efficiently transfer and stably express foreign genes in isolated lapine and human meniscal cells in vitro and in lapine meniscal defects in vivo.

Clinical Relevance

This direct gene transfer approach may form a basis for improved treatments of meniscal tears.