Kidney Subcapsular Allograft Transplants as a Model to Test Virus-Derived Chemokine-Modulating Proteins as Therapeutics

Michelle Burgin, Jordan Yaron, Liqiang Zhang, Qiuyun Guo, Juliane Daggett, Jacquelyn Kilbourne, Kenneth M. Lowe, Alexandra R. Lucas

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Solid tissue transplant is a growing medical need that is further complicated by a limited donor organ supply. Acute and chronic rejection occurs in nearly all transplants and reduces long-term graft survival, thus increasing the need for repeat transplantation. Viruses have evolved highly adapted responses designed to evade the host’s immune defenses. Immunomodulatory proteins derived from viruses represent a novel class of potential therapeutics that are under investigation as biologics to attenuate immune-mediated rejection and damage. These immune-modulating proteins have the potential to reduce the need for traditional posttransplant immune suppressants and improve graft survival. The myxoma virus-derived protein M-T7 is a promising biologic that targets chemokine and glycosaminoglycan pathways central to kidney transplant rejection. Orthotopic transplantations in mice are prohibitively difficult and costly and require a highly trained microsurgeon to successfully perform the procedure. Here we describe a kidney-to-kidney subcapsular transplant model as a practical and simple method for studying transplant rejection, a model that requires fewer mice. One kidney can be used as a donor for transplants into six or more recipient mice. Using this model there is lower morbidity, pain, and mortality for the mice. Subcapsular kidney transplantation provides a first step approach to testing virus-derived proteins as new potential immune-modulating therapeutics to reduce transplant rejection and inflammation.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages257-273
Number of pages17
DOIs
StatePublished - 2021

Publication series

NameMethods in Molecular Biology
Volume2225
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Immunomodulatory
  • Rejection
  • Renal
  • Therapeutics
  • Transplant
  • Viral protein

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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