The effects of long-term gene transfer of an apoptosis inducer such as FasL on the chondrocytes in cartilage in vivo require further investigation.
Our study elucidates firstly the in vivo therapeutic potential of molecular synovectomy using 'gene scalpels' for the treatment of RA locally through repeated intra-articular gene transfer of an apoptosis inducer.
In summary, our in vivo investigation of gene transfer to human synovium in SCID mice suggests that repeated intra-articular gene transfer of an apoptosis inducer, such as FasL, may function as a 'gene scalpel' for molecular synovectomy to arrest inflammatory synovium at an early stage of RA.
A novel experimental system incorporating the grafting of RA synovial tissue into severe combined immunodeficiency (SCID) mice [ 20- 22] has provided an in vivo model for the evaluation of our hypothesis; the repeated gene transfer of an apoptosis inducer such as FasL, mediated by an efficient vehicle, might function as a gene scalpel for the removal of inflammatory synovium in situ.
To test this possibility, a dominant negative form of p73β (ΔN-p73β) was expressed in the p65 reconstituted cells by retroviral transfer and the level of apoptosis following etoposide treatment determined.
This study was designed to assess the efficacy of in vivo viral gene transfer of the antiapoptotic factor apoptosis repressor with caspase recruitment domain to block apoptosis and preserve ventricular geometry and function.
Also, adenoviral FasL gene transfer induced apoptosis of the synoviocytes and markedly ameliorated CIA in mice [ 73].
Next, to determine whether the bystander cytotoxicity is because of apoptosis, CM transfer experiments were performed.
Clinical trials of p53 gene therapy for lung cancer[ 1*, 12*] have been reported, and these studies demonstrate gene transfer of adenoviral-p53, induction of apoptosis, and some indication of therapeutic response.
To evaluate the apoptotic effects of miR-92 in our adoptive transfer model in vivo, we collected premalignant Eμ-myc B-cells from spleen or bone marrow of well-controlled Eμ-myc/92 and Eμ-myc/MSCV mice at 5 weeks after adoptive transfer and measured the extent of apoptosis by FACS.
