AI Article Synopsis
- Decreasing blood donation rates have created a need for alternative sources, leading to the exploration of genetically engineered pig red blood cells (pRBCs), particularly triple-gene knockout (TKO) versions, for human transfusion compatibility.
- In a study involving nonhuman primates, both wild-type (WT) and TKO-pRBC transfusions significantly improved red blood cell counts initially, but triggered the body's immune response, leading to rapid antibody production and liver function impairment.
- While initial hematological improvements were noted on the first day post-transfusion, both pRBC types showed diminished circulation benefits and increased adverse reactions upon subsequent transfusions, raising concerns about their long-term efficacy in humans.
Article 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 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236543 | PMC |
| http://dx.doi.org/10.3389/fimmu.2024.1418249 | DOI Listing |
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