Home Articles & Issues Editor's Picks Collections Videos For Authors Journal Info
Skip Navigation LinksHome > February 27, 2014 - Volume 97 - Issue 4 > A Human-Specific Mutation Limits Nonhuman Primate Efficacy i...
Transplantation:
doi: 10.1097/01.TP.0000441321.87915.82
Rapid Communication

A Human-Specific Mutation Limits Nonhuman Primate Efficacy in Preclinical Xenotransplantation Studies

Waldman, Joshua P.1; Brock, Linda G.1; Rees, Michael A.1,2

Collapse Box

Abstract

Background

Patients diagnosed with fulminant hepatic failure face high mortality rates. A potential therapeutic approach for these patients is the use of extracorporeal porcine liver perfusion, to serve as a form of “liver dialysis.” Previously, our laboratory has shown that, during a 72-hour extracorporeal perfusion with human blood, porcine Kupffer cells bind to and phagocytose human erythrocytes causing the hematocrit to fall to 2.5% of the original value. Subsequently, erythrocyte binding has been shown to involve N-acetylneuraminic acid (Neu5Ac) on the surface of human erythrocytes and sialoadhesin on the surface of the porcine Kupffer cells.

Methods

Given that no primate other than the human is known to express the majority of its sialic acid as Neu5Ac, we evaluated whether nonhuman primates would provide adequate evaluation of the loss of erythrocytes that might be expected in a clinical trial of extracorporeal porcine liver perfusion.

Results

We found that while porcine macrophages readily bound human erythrocytes, binding of nonhuman primate erythrocytes was significantly reduced (P<0.001).

Conclusions

This study suggests that nonhuman primates may fail to serve as an adequate model for studying extracorporeal porcine liver perfusion because of the fact that porcine macrophages do not bind nonhuman primate erythrocytes.

Copyright © 2014 by Lippincott Williams & Wilkins

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.