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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:2225

Enthalten in:

Methods in molecular biology (Clifton, N.J.) - 2225(2021) vom: 27., Seite 257-273

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

80295-50-7
80295-52-9
Anti-Inflammatory Agents
Biomarkers
Chemokines
Complement C4b
Complement C4d
Immunologic Factors
Immunomodulatory
Journal Article
M-T7 protein, Myxoma virus
Peptide Fragments
Receptors, Interferon
Recombinant Proteins
Rejection
Renal
Therapeutics
Transplant
Viral Proteins
Viral protein

Anmerkungen:

Date Completed 26.03.2021

Date Revised 26.03.2021

published: Print

Citation Status MEDLINE

doi:

10.1007/978-1-0716-1012-1_15

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM316773387