Treg-inducing microparticles promote donor-specific tolerance in experimental vascularized composite allotransplantation

• DOI: 10.1073/pnas.1910701116
• Publication Date: 2019-12-03T01:26:54Z
• Authors: James D. Fisher; Stephen C. Balmert; Wensheng Zhang; Riccardo Schweizer; Jonas T. Schnider; Chiaki Komatsu; Liwei Dong; Vasil E. Erbas; Jignesh V. Unadkat; Ali Mübin Aral; Abhinav P. Acharya; Yalcin Kulahci; Heth R. Turnquist; Angus W. Thomson; Mario G. Solari; Vijay S. Gorantla; Steven R. Little
• Keywords: Immunosuppression Therapy; Vascularized Composite Allotransplantation; 0301 basic medicine; 1000 Multidisciplinary; 610 Medicine & health; T-Lymphocytes, Regulatory; Rats; 3. Good health; 03 medical and health sciences; Drug Delivery Systems; Cell-Derived Microparticles; Animals; Cytokines; Transplantation Tolerance; 10266 Clinic for Reconstructive Surgery; Immunosuppressive Agents

Significance Vascularized composite allotransplantation (VCA) is an emerging field that is particularly beneficial for select amputees and patients with devastating soft tissue loss that is not amenable to conventional reconstructive surgeries. As with solid organ transplantation, VCA recipients are subjected to a lifelong regimen of antirejection drugs with a well-established sequela. Herein, we report a synthetic, controlled-release microparticle system (referred to as TRI-MP) that aims to locally enrich naturally occurring, suppressive lymphocytes to prevent allograft rejection and promote tolerance. While this study exclusively focuses on VCA, this technology has implications for other conditions characterized by aberrant inflammation.