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17. The Role of the Alternative Complement Pathway in Early Graft Loss After Intraportal Porcine Islet Xenotransplantation

Author

Kang, Hee Jung, primary, Lee, Haneulnari, additional, Ha, Jeong-mi, additional, Lee, Jae-il, additional, Shin, Jun-Seop, additional, Kim, Ki-Yong, additional, Park, Ji Yoon, additional, Kim, Jung-Sik, additional, Min, Sang Il, additional, Park, Chung-Gyu, additional, Park, Seong Hoe, additional, and Kim, Sang Joon, additional

Published
2014
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22. Investigation of the efficacy and safety of wild- type and triple-gene knockout pig RBC transfusions in nonhuman primates.

Author

Roh J, Hwang JH, Park S, Lee H, Park EM, Lee HW, Lee JY, Shim J, Choi K, and Kang HJ

Subjects
Animals, Swine, Animals, Genetically Modified, Hemoglobins metabolism, Galactosyltransferases genetics, Galactosyltransferases deficiency, Hematocrit, Female, Male, Primates, Erythrocyte Transfusion adverse effects, Erythrocyte Transfusion methods, Gene Knockout Techniques, Erythrocytes immunology, Erythrocytes metabolism
Abstract

Introduction: Decreasing rates of blood donation and close margins between blood supply and demand pose challenges in healthcare. Genetically engineered pig red blood cells (pRBCs) have been explored as alternatives to human RBCs for transfusion, and triple-gene knockout (TKO) modification improves the compatibility of pRBCs with human blood in vitro . In this study, we assessed the efficacy and risks of transfusing wild-type (WT)- and TKO-pRBCs into nonhuman primates (NHPs)., Methods: Blood from O-type WT and TKO pigs was processed to produce pRBCs for transfusion, which were transfused or not into NHPs (n=4 per group: WT, TKO, and control) after 25% total blood volume withdrawal: their biological responses were compared. Hematological, biochemical, and immunological parameters were measured before, immediately after, and at intervals following transfusion. Two months later, a second transfusion was performed in three NHPs of the transfusion group., Results: Transfusion of both WT- and TKO-pRBCs significantly improved RBC counts, hematocrit, and hemoglobin levels up to the first day post-transfusion, compared to the controls. The transfusion groups showed instant complement activation and rapid elicitation of anti-pig antibodies, as well as elevated liver enzyme and bilirubin levels post-transfusion. Despite the higher agglutination titers with WT-pRBCs in the pre-transfusion crossmatch, the differences between the WT and TKO groups were not remarkable except for less impairment of liver function in the TKO group. After the second transfusion, more pronounced adverse responses without any hematological gain were observed., Conclusions: WT- and TKO-pRBC transfusions effectively increased hematologic parameters on the first day, with rapid clearance from circulation thereafter. However, pRBC transfusion triggers strong antibody responses, limiting the benefits of the pRBC transfusion and increasing the risk of adverse reactions., Competing Interests: Authors JS and KC are employed by the company Optipharm Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Roh, Hwang, Park, Lee, Park, Lee, Lee, Shim, Choi and Kang.)

Published
2024
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