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Transgene Expression in a Model of Composite Tissue Allotransplantation

Cooney, Damon S. M.D., Ph.D.; Chambers, Christopher B. Ph.D.; Suchy, Hans M.S.; Hornick, M. Christine B.S.; Reichensperger, Joel B.S.; Neumeister, Michael W. M.D.

Plastic & Reconstructive Surgery: March 2010 - Volume 125 - Issue 3 - pp 837-845
doi: 10.1097/PRS.0b013e3181cb6389
Experimental: Original Articles

Background: Composite tissue allografting may be an ideal solution to many problems requiring reconstructive surgery. Unfortunately, complications associated with chronic immunocompromise are major impediments to widespread use of composite tissue allografting. Current immunosuppressive and immunomodulatory paradigms focus on modification of the recipient through global immunosuppression or donor/recipient chimerism. Alternatively, modifying the allograft to block rejection or promote tolerance could confine deleterious immunosuppressive effects to the graft or eliminate graft rejection. However, a technique introducing genetic information into the transplant is needed. The authors demonstrate the first model for expressing a gene of interest locally in a hind-limb transplant.

Methods: Using a rat hind-limb transplant model, the authors tested the ability of naked DNA infusion, cationic polymer/DNA complex transfection, and adenoviral vector transduction to introduce genetic material into the composite tissue allograft. The marker genes luciferase and green fluorescent protein were used to follow gene expression.

Results: Recombinant adenovirus showed rapid, high-level expression of marker genes in the graft, with no detectable expression in recipient animals. Expression was detectable at 18 hours and peaked at 7 days. Levels of expression were lower but above baseline at 4 weeks.

Conclusions: Using an adenoviral vector system, the authors have selectively introduced a marker gene (luciferase) into a transplanted hind-limb rat model. Expression was rapid and seen in a variety of cell types. Adenovirus infection had no impact on limb rejection. This method may be a powerful tool for genetically modifying composite tissue allografts and may contribute to immune tolerance and more widespread use of composite tissue allograft surgery.

Springfield, Ill.

From the Plastic Surgery Institute, Southern Illinois University School of Medicine.

Received for publication May 29, 2009; accepted September 25, 2009.

Presented at the Annual Meeting of the American Society of Reconstructive Microsurgery, in Beverly Hills, California, January 12 through 15, 2008; the Midwestern Association of Plastic Surgeons, in Chicago, Illinois, May of 2008; the Southern Illinois University Department of Surgery Resident Research Day, in Springfield, Illinois, May of 2008; and the 62nd Annual Meeting of the Canadian Society of Plastic Surgeons, in St. John's, Newfoundland and Labrador, Canada, June 25 through 28, 2008.

Disclosures: This project was supported in part by research grants from Southern Illinois University School of Medicine Department of Surgery, the Plastic Surgery Educational Foundation, the Memorial Medical Center Memorial Foundation, and the American Association for Hand Surgery. None of the authors has any commercial associations or financial interests that might pose a conflict of interest with this work.

Damon S. Cooney, M.D., Ph.D.; The Plastic Surgery Institute; Southern Illinois University School of Medicine; P.O. Box 19653; Springfield, Ill. 62794-9653; dcooney@siumed.edu

©2010American Society of Plastic Surgeons