PDF(Pubmed)
Abstract：
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■献血率的下降以及血液供应和需求之间的差距对医疗保健构成了挑战。基因工程猪红细胞（pRBC）已被探索作为人类红细胞输血的替代品，三基因敲除（TKO）修饰可改善pRBC与人血液的相容性。在这项研究中,我们评估了向非人灵长类动物(NHP)输注野生型(WT)-和TKO-pRBC的疗效和风险.
■将来自O型WT和TKO猪的血液加工以产生用于输血的pRBC，已输注或未输注到NHP中（每组n=4：WT，TKO,和对照）在25％的总血容量撤出后：比较了它们的生物学反应。血液学,生物化学，之前测量了免疫学参数，紧接着,输血后的时间间隔。两个月后,在输血组的3个NHP中进行了第二次输血.
■WTC和TKO-pRBC的输血显著提高了红细胞计数，血细胞比容,输血后第一天的血红蛋白水平，与对照组相比。输血组显示即时补体激活和快速激发抗猪抗体，以及输血后肝酶和胆红素水平升高。尽管在输血前交叉配血中WT-pRBC的凝集滴度较高，WT组和TKO组之间的差异不显著,但TKO组肝功能受损较少.第二次输血后,观察到更明显的不良反应,无任何血液学增益.
■在第一天，WTT和TKO-pRBC输血有效地增加了血液学参数，此后从循环中快速清除。然而,pRBC输血引发强抗体反应，限制pRBC输血的益处并增加不良反应的风险。
■将来自O型WT和TKO猪的血液加工以产生用于输血的pRBC，已输注或未输注到NHP中（每组n=4：WT，TKO,和对照）在25％的总血容量撤出后：比较了它们的生物学反应。血液学,生物化学，之前测量了免疫学参数，紧接着,输血后的时间间隔。两个月后,在输血组的3个NHP中进行了第二次输血.
■WTC和TKO-pRBC的输血显著提高了红细胞计数，血细胞比容,输血后第一天的血红蛋白水平，与对照组相比。输血组显示即时补体激活和快速激发抗猪抗体，以及输血后肝酶和胆红素水平升高。尽管在输血前交叉配血中WT-pRBC的凝集滴度较高，WT组和TKO组之间的差异不显著,但TKO组肝功能受损较少.第二次输血后,观察到更明显的不良反应,无任何血液学增益.
■在第一天，WTT和TKO-pRBC输血有效地增加了血液学参数，此后从循环中快速清除。然而,pRBC输血引发强抗体反应，限制pRBC输血的益处并增加不良反应的风险。
