Correlation of Chimerism With Graft Size and Revascularization in Vascularized and Nonvascularized Skin Allografts

Abstract

The high antigenicity of skin components of composite tissue allografts is the most challenging factor in achieving long-term viability after composite tissue allografts transplantation. The vascularization pattern of vascularized skin allografts (VSA) and nonvascularized skin allografts (NVSA) differs significantly and these differences may alter host immune responses. We hypothesized that vascularized grafts contribute to better engraftment and long-term survival. We have tested our hypothesis by transplantation of different sizes (2 x 2 cm, 4 x 4 cm, 6 x 6 cm) of VSA and NVSA across major histocompatibility complex barrier between LBN (RT1(1+n)) and Lewis (RT1(1)) rats. Correlation of revascularization process with development of donor-specific chimerism was tested. We found that the highest chimerism levels (8%-12.2% in VSA groups; 2.53%-3.92% in NVSA groups) were reached as early as 7 days in both VSA and NVSA. Chimerism decreased in both groups during 100-day follow-up and higher chimerism was found only in VSA in late posttransplant period. Revascularization, assessed by the presence of CD31 positive vessels, was significantly higher in VSA compared with NVSA and to controls (P < 0.05). A direct correlation was seen between increased skin diameter and donor chimerism in VSA, whereas inverse correlation was tested in NVSA. We have confirmed that allograft size and vascularization pattern contribute to donor chimerism development and maintenance.

Evidence That FoxP3+ Regulatory T Cells May Play a Role in Promoting Long-Term Acceptance of Composite Tissue Allotransplants

“…These findings are similar to our previous experience (17) and that of others (23). Throughout the 150 day follow-up period, the CTA acceptor animals demonstrated functional donor-specific tolerance, whereas animals with chimerism levels less than 1% rejected their CTA grafts.…”

Lessons Learned From the First Quadruple Extremity Transplantation in the World

“…3 The aim of our experimental studies is to achieve permanent immune tolerance without the use of immunosuppressive drugs and develop novel clinical composite tissue allotransplantations in the future. 4,5 Nerve allotransplantations in replanted arms have been performed by the authors on 2 children, the younger of whom had total motor and sensorial recovery. To our knowledge, this report on clinical nerve allotransplantation was the second published article in the literature.…”

Concomitant Face and Hand Transplantation

“…Although clinically, we have seen no difference in rejection between wrist-level hand transplants as compared with higher levels (ie, elbow-level, shoulder-level) with more skin, there are several conflicting studies indicating amplified immunologic responses with increased antigenic skin loads. [15][16][17][18] For instance, abdominal wall transplants contain large skin/muscle components and accompany no underlying bone. In contrast, CTAs containing bone, such as osteocutaneous face and hand, may contain a tolerogenic advantage analogous to vascularized bone marrow transplantation, 19,20 which is present in osteocutaneous face and hand transplants.…”