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Emulating Nature's Genius: Engineered Biomimetic Formulations for Suppressing Rejection in Vascularized Composite Allotransplantation
James D. Fisher, Jignesh V. Unadkat, Riccardo Schweizer,
Chiaki Komatsu, Sinan Oksuz, Mario G. Solari, Vijay S. Gorantla, Steven R. Little
University of Pittsburgh
2014-03-14
Presenter: James D. Fisher
Affidavit:
This material has not been presented at a major meeting or published and represents the original work of the presenting student (James Fisher) with guidance from the mentorship team (Little, Gorantla, Solari) and assistance from the surgical team (Unadkat, Schweizer, Komatsu).
Director Name: Steven R. Little
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: Hand
Vascularized composite allotransplantation (VCA)-encompassing transplantation of hands/limbs and face is an emerging field with potential to restore the appearance and function of damaged tissue. Clinically, the process of rejection is suppressed via systemic immunosuppression, which is associated with a host of deleterious side effects. An alternative approach to prevent rejection is to harness the homeostatic mechanisms intrinsic to the immune system. To this end our group has recently developed controlled release microparticle (MP) systems capable of enriching suppressive lymphocytes (known as Regulatory T Cells or Tregs) at given location via synthetic constructs referred to as Expansion MP. Accordingly, we hypothesized that Treg enriching systems that release key cytokines, and immunosuppressive agents, can promote long term graft survival in preclinical VCA models. Following fabrication, Expansion MP was tested first in an allogeneic rat hind limb transplant model and next in a swine gracilis myocutaneous flap allotransplant model. Following subcutaneous injection of microparticles, rodent hind limbs survived indefinitely (>300 days) and swine allografts were able to survive 3 weeks with no signs of rejection, with controls rejecting at days 7-9. Secondary skin grafts and MLRs in the rodent model demonstrate that ExpansionMP treatment appears to confer donor specific tolerance to recipients. Given these promising results, we believe this technology has the potential to dramatically impact the field of VCA and reconstructive transplantation.
