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Updated: May 3, 2026
Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells
Published on: February 15, 2019
A human-specific mutation limits nonhuman primate efficacy in preclinical xenotransplantation studies
Joshua P Waldman1, Linda G Brock, Michael A Rees
11 Department of Urology, University of Toledo Medical Center, Toledo, OH. 2 Address correspondence to: Michael A. Rees, M.D., Ph.D., University of Toledo Medical Center, Department of Urology, Mail Stop 1091, 3000 Arlington Avenue, Toledo, OH 43614.
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.
