Inhibition of Lymphatic Drainage With a Self-Designed Surgical Approach Prolongs the Vascularized Skin Allograft Survival in Rats

Abstract

Vascularized composite allotransplantation (VCA) is an emerging treatment for significant tissue defects. However, VCAs usually consist of multiple highly antigenic skin tissues. Previous studies have shown that the lymphatic system in skin plays important roles in the initiation of immune responses during acute rejection, by transporting T cells and antigen-presenting dendritic cells to regional lymph nodes. Therefore, we designed a new surgical treatment to inhibit lymphatic drainage of skin allografts and investigated whether this approach could promote the survival of allografts and suppress immunological events after transplantation. This procedure was achieved by connecting the vascularized allografts to recipient tissues with only an annular plastic holder, allowing the minimum of allograft contact with recipients. Our results showed that the self-designed treatment for inhibiting lymphatic drainage promoted the survival of allografts, reduced the serum concentration of IL-2, and decreased the percentage of CD4CD25 and CD8CD25 from the lymphatic nodes draining the transplantation region. In conclusion, these data suggest that self-designed surgical approach is effective in inhibiting lymphatic drainage of skin allografts, and the lymphatic system may be new therapeutic targets for developing techniques or drugs against acute rejection after VCAs.

Vascularized composite allotransplants as a mechanistic model for allograft rejection – an experimental study

“…The capacity to isolate these peripheral and central modes of allosensitization can facilitate and trigger further experiments in VCA focusing on the manipulation of regional lymphatics and its effect on allograft outcomes. The latter is a subject of ongoing research in the field [16,17]. Several studies have demonstrated the critical nature of secondary lymphoid organs in organ allograft rejection.…”