Large Antigenic Skin Load in Total Abdominal Wall Transplants Permits Chimerism Induction

Abstract

The application of composite tissue allograft (CTA) transplants in clinical reconstruction is parallel with extended knowledge of anatomy, microsurgical skills and development of transplantation immunology. CTAs are composed of multiple tissues, some of which such as skin are highly immunogenic and cause strong immunologic responses. Strong antigenic nature of skin may be related to Langerhans cells, which are powerful antigen-presenting cells. They are leukocytes found in the epidermis as members of immunologic cascade. Large skin components of CTA transplant may cause higher antigenic load as a result of increased surface area of transplanted skin correlating with increased load of Langerhans cells. In clinical abdominal wall transplants, increased rejection episodes were reported compared with other CTA transplant. This complication may correlate to large skin component of these transplants. To evaluate correlation between large skin island flaps and immunologic responses, CTA models with large skin components should be tested in experimental studies. Here we propose a total abdominal wall (TAW) transplant model in rat to test the feasibility of TAW transplantation in 2 groups: the anatomic study and experimental transplantation group. In anatomic study, TAW flaps were elevated bilaterally on superficial epigastric vessels and replaced. The entire TAW skin islands of all flaps were viable at postoperative day 21. Dye study confirmed that TAW flap was supplied by 2 vascular pedicles. Data in this group demonstrated that this flap is composed of the largest skin island when compared with other CTA transplant models such as full face, hemiface, limb, and groin flap. In experimental group, isograft transplantations were performed between Lewis rats (RT1(1)) while allograft transplantations were performed Lewis (RT1(1)) donors and LBN (RT(1+n)) recipients. All TAW transplants showed viable islands at posttransplant day 200 under cyclosporine A monotherapy protocol. Microangiography of the transplant demonstrated entire skin island was supplied bilaterally by superficial epigastric vessels pedicle. Dye studies with India ink demonstrated dye uptake in all flap components. Histologic examination also demonstrated the viability of flap tissues. High chimerism levels in peripheral blood was determined at the 7th, 21st, 35th, 63rd, and 100th posttransplant days was compared with full face, hemiface, groin flap data. It was found that TAW transplant had higher chimerism level compared with groin flap but lower chimerism than full face and hemiface allografts. TAW transplant may serve as a new experimental model with large skin component and may be useful to determine immunologic responses to tissues with high antigenic load under different immunosuppressive protocols.