Genetically engineered pig red blood cells for clinical transfusion: initial in vitro studies
Cassandra Long
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorHidetaka Hara
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorZachary Pawlikowski
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorNaoko Koike
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorThomas D'Arville
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorPeter Yeh
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorMohamed Ezzelarab
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorDavid Ayares
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorMark Yazer
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorDavid K.C. Cooper
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorCassandra Long
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorHidetaka Hara
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorZachary Pawlikowski
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorNaoko Koike
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorThomas D'Arville
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorPeter Yeh
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorMohamed Ezzelarab
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorDavid Ayares
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorMark Yazer
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorDavid K.C. Cooper
From the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and Revivicor, Inc., Blacksburg, Virginia.
Search for more papers by this authorCL and HH contributed equally. MY and DKCC are joint senior authors.
Abstract
BACKGROUND: Pigs are a potential source of red blood cells (RBCs) and could resolve the shortage of human blood for transfusion. This study investigated in vitro the compatibility of genetically engineered pig RBCs (pRBCs) with the human innate immune response.
STUDY DESIGN AND METHODS: Human volunteers of all ABO blood types were sources of sera and those of O blood type were sources of circulating monocytes/macrophages. RBCs from ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) humans and wild-type (WT) and α-1,3-galactosyltransferase gene-knockout (GTKO) pigs were tested for hemagglutination, immunoglobulin (Ig)M/IgG antibody binding, and complement-dependent cytotoxicity (CDC) using human sera. Phagocytosis of RBCs by human monocyte–derived macrophages was measured by coculture in the absence or presence of pooled human O serum.
RESULTS: RBCs showed significant differences (p < 0.01) with regard to hemagglutination, IgM and IgG binding, and CDC (ABO-C < GTKO < ABO-I < WT). In the absence of pooled human O serum (antibodies), there was no phagocytosis of any RBCs; in the presence of serum (antibodies), phagocytosis of ABO-I RBCs was greater than of WT (p < 0.01), which in turn was greater than of GTKO RBCs (p < 0.05).
CONCLUSIONS: GTKO RBCs were significantly more compatible than ABO-I and WT RBCs, but were not comparable to ABO-C combinations. In the presence of antibody, human monocyte–derived macrophages phagocytosed ABO-I RBC/sera combinations more efficiently than pRBCs. These observations contribute to our ultimate goal of using genetically engineered pRBCs for clinical blood transfusion. However, pigs will require other modifications or manipulations if they are to become suitable for human transfusion.
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