Immunological organ modification during Ex Vivo machine perfusion: The future of organ acceptance.

Journal Article (Journal Article;Review)

Ex vivo machine perfusion (EVMP) has gained revitalized interest in recent years due to the increasing use of marginal organs which poorly tolerate the standard preservation method static cold storage (SCS). EVMP improves on SCS in a number of ways, most notably by the potential for reconditioning of the donor organ prior to transplantation without the ethical concerns associated with organ modulation before procurement. Immunomodulatory therapies administered during EVMP can influence innate and adaptive immune responses to reduce production of inflammatory molecules and polarize tissue-resident immune cells to a regulatory phenotype. The targeted inhibition of an inflammatory response can reduce ischemia-reperfusion injury following organ reoxygenation and therefore reduce incidence of graft dysfunction and rejection. Numerous approaches to modulate the inflammatory response have been applied in experimental models, with the ultimate goal of clinical translatability. Strategies to target the innate immune system include inhibiting inflammatory signaling pathways, upregulating anti-inflammatory mediators, and decreasing mitochondrial damage while those which target the adaptive immune system include mesenchymal stromal cells. Inhibitory RNA approaches target both the innate and adaptive immune systems with a focus on MHC knock-down. Future studies may address issues of therapeutic agent delivery through use of nanoparticles and explore novel strategies such as targeting co-inhibitory molecules to educate T-cells to a tolerogenic state. In this review, we summarize the cellular and acellular contributors to allograft dysfunction and rejection, discuss the strategies which have been employed pre-clinically during EVMP to modulate the donor organ immune environment, and suggest future directions for immunomodulatory EVMP studies.

Full Text

Duke Authors

Cited Authors

  • Carlson, K; Barbas, A; Goldaracena, N; Fernandez, L; Al-Adra, DP

Published Date

  • April 2021

Published In

Volume / Issue

  • 35 / 2

Start / End Page

  • 100586 -

PubMed ID

  • 33876730

Electronic International Standard Serial Number (EISSN)

  • 1557-9816

Digital Object Identifier (DOI)

  • 10.1016/j.trre.2020.100586

Language

  • eng

Conference Location

  • United States