Patients who will be recruited for this study will only be those with a clinical 
indication for the staged removal of synovium from multiple diarthrodial joint(s) 
including 2nd-5th MCP joint arthroplasty. For example, the patient who eventually 
receives the 2nd-5th MCP joint arthroplasty may have a clinical indication for ipsilateral 
and/or contralateral therapeutic wrist synovectomy, or total elbow, knee, or hip 
arthroplasty at which time ample amounts of synovium (in addition to what might be 
sent for histopathological analysis) will be obtained and sent to the laboratory for culture 
and genetic modification. Since this procedure would have been performed anyway, the 
patient has not yet been affected by participating in this study. 
At an appropriate time, probably 6 weeks to 3 months after the synovium has 
been collected, reimplantation of the modified cells will occur. Synoviocytes which have 
been successfully transduced with DFG-IRAP-tk, and which show high expression of 
IRAP and sensitivity to ganciclovir in vitro, will be returned by intraarticular injection to 
2 out of 4 of the patients' MCP joints scheduled for joint replacement. The other 2 
MCP joints will receive back untransduced cells as controls. The study subject will visit 
Dr. Herndon's office one week prior to the scheduled 2nd-5th MCP joint arthroplasty. 
During this visit, the patient's autologous modified synoviocytes will be returned by 
intraarticular injection into the MCP joints. Two MCP joints will receive cells 
transduced with the IRAP and tk genes. The other two MCP joints will serve as controls 
and receive unmodified cells. Prior to reimplantation, cells will be harvested by 
trypsinizing, thoroughly washed in saline solution, and resuspended at a concentration of 
2x10^ cells per ml in saline solution. 
At the time of reimplantation, each MCP joint will first be lavaged with 1ml of 
saline solution. If the intraarticular injection is excessively distressing, dorsal radial and 
dorsal ulnar nerve block will be performed using local anesthetic. In-office injections of 
any sort will be performed under scrupulously sterile conditions. After lavage, the barrel 
of the syringe will be removed leaving the 27G needle in place. A fresh barrel 
containing 0.5ml of the appropriate cell suspension will then be attached to the needle, 
permitting intraarticular injection of the cells. Aside from follow-up blood drawing 
described below, this will be the only extra procedure that patients will undergo as a 
result of this study . 
As scheduled, the patient will undergo 2nd-5th MCP joint arthroplasty of those 
joints which had been manipulated one week previously. During this procedure, the 
joints will again be lavaged with 1ml of saline. Synovium/sub-synovium/adjacent joint 
capsule will be surgically removed and placed in their respective, clearly labeled, sterile 
containers for transport to the appropriate laboratory. The 2nd-5th MCP joint 
arthroplasty procedure will be approached in a manner identical to that used for tumor 
cases. Caution will be taken to thwart contamination of the surrounding tissues with 
joint contents. All OR personnel and couriers will be properly advised to the 
significance of the samples being sent to the laboratory. Solid tissues will be sent in 
sterile saline promptly to the laboratory. 
Recombinant DNA Research, Volume 19 
[431] 
