Old World Monkeys are less than ideal transplantation models for testing pig organs lacking three carbohydrate antigens (Triple-Knockout)
Old World Monkeys are less than ideal transplantation models for testing pig organs lacking three carbohydrate antigens (Triple-Knockout)
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DOI：
10.1038/s41598-020-66311-3
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发表时间：
2020-06-17
影响因子：
4.6
通讯作者：
Hara, Hidetaka
中科院分区：
文献类型：
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作者：
Yamamoto, Takayuki;Iwase, Hayato;Hara, Hidetaka
三敲除（TKO）猪（添加保护性人类转基因）可能是临床器官异种移植的最佳器官来源，因为许多人对TKO猪细胞只有很少或没有天然抗体。然而，旧大陆猴（OWMs）具有天然存在的针对TKO细胞的抗体。我们使用人类、几只OWMs和两只新世界猴（NWMs）的血清检测了抗猪IgM/IgG结合以及补体依赖性细胞毒性对野生型（WT）、α 1,3-半乳糖转移酶基因敲除（GTKO）和TKO猪外周血单个核细胞（PBMCs）的影响。此外，我们比较了GTKO （n=5）和TKO （n=3）猪肾脏在狒狒体内的存活率。与人类或NWMs相比，OWMs对TKO PBMCs具有更强的IgM结合和细胞毒性。平均抗tko IgM在OWMs中显著高于人类，在NWMs中显著低于人类。OWM血清对TKO PBMCs的细胞毒性显著高于人血清，而人血清与NWM血清之间无显著差异。TKO猪肾脏在狒狒体内的中位生存期（4天）明显短于GTKO肾脏（136天）（p . 591）
Triple-knockout (TKO) pigs (with added protective human transgenes) are likely to be optimal sources of organs for clinical organ xenotransplantation because many humans have minimal or no natural antibody to TKO pig cells. However, Old World monkeys (OWMs) have naturally-existing antibodies directed to TKO cells. We measured anti-pig IgM/IgG binding, and complement-dependent cytotoxicity to wild-type (WT), alpha 1,3-galactosyltransferase gene-knockout (GTKO), and TKO pig peripheral blood mononuclear cells (PBMCs) using sera from humans, several OWMs, and two New World monkeys (NWMs). Furthermore, we compared survival of GTKO (n=5) and TKO (n=3) pig kidneys in baboons. OWMs had significantly greater IgM binding and cytotoxicity to TKO PBMCs than humans or NWMs. Mean anti-TKO IgM was significantly higher in OWMs and significantly lower in NWMs than in humans. Cytotoxicity of OWM sera to TKO PBMCs was significantly greater than of human serum, but there was no significant difference between human and NWM sera. The median survival of TKO pig kidneys (4 days) in baboons was significantly shorter than that of GTKO kidneys (136 days) (p