Erythropoietic properties of human induced pluripotent stem cells-derived red blood cells in immunodeficient mice.
Erythropoietic properties of human induced pluripotent stem cells-derived red blood cells in immunodeficient mice.
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免疫缺陷小鼠中人类诱导多能干细胞的红细胞衍生的红细胞的红细胞生成特性。
DOI：
10.1002/ajh.26410
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发表时间：
2022-02-01
影响因子：
12.8
通讯作者：
Roback JD
中科院分区：
文献类型：
--
作者：
Deng J;Lancelot M;Jajosky R;Deng Q;Deeb K;Saakadze N;Gao Y;Jaye D;Liu S;Stowell SR;Cheng L;Roback JD
输注红细胞（RBC）是贫血患者的救命措施。人诱导多能干细胞（iPSC）具有扩增和分化成RBC（iPSC-RBC）的能力。在此，我们开发了鼠模型以研究人iPSC-RBC的体内特性。通过瞬时表达含有0 CT 4、S 0X 2、MYC、KLF 4和BCL-XL基因的质粒，从人外周血单核细胞产生iPSC系。人iPSC-RBC在补充有人血小板裂解物的培养物中产生，并且是CD 34 − CD 235 a + CD 233 + CD 49 dlow CD 71 low;约13%的iPSC-RBC在输血前被去核。向NOD scid gamma（NSG）小鼠全身施用氯膦酸盐脂质体（CL）和眼镜蛇毒因子（CVF）显著促进了输血后人iPSC-RBC的循环存活。虽然iPSC-RBC随着时间的推移而逐渐减少，但90%的循环iPSC-RBC在输血后1天被去核（CD 235 a + CD 233 + CD 49 d − CD 71 −）。令人惊讶的是，人iPSC-RBC在输血后3周以比输血后1小时高8倍以上的水平再次出现在外周循环中。此外，大部分输注的有核iPSC-RBC优先归巢至骨髓，并且在输注后24天可检测到。这些结果表明，归巢至NSG小鼠骨髓的有核人iPSC衍生细胞保留了完全分化成去核红细胞并将骨髓排出到外周血中的能力。这些结果提供了一种使用人外周血来源的iPSC和CL/CVF处理的NSG小鼠来研究体内人红系细胞的发育和循环的新模型。
Transfusion of red blood cells (RBCs) is a life-saving intervention for anemic patients. Human induced pluripotent stem cells (iPSC) have the capability to expand and differentiate into RBCs (iPSC-RBCs). Here we developed a murine model to investigate the in vivo properties of human iPSC-RBCs. iPSC lines were produced from human peripheral blood mononuclear cells by transient expression of plasmids containing OCT4, SOX2, MYC, KLF4, and BCL-XL genes. Human iPSC-RBCs were generated in culture supplemented with human platelet lysate, and were CD34−CD235a+ CD233+ CD49dlow CD71low; about 13% of iPSC-RBCs were enucleated before transfusion. Systemic administration of clodronate liposomes (CL) and cobra venom factor (CVF) to NOD scid gamma (NSG) mice markedly promoted the circulatory survival of human iPSC-RBCs following transfusion. While iPSC-RBCs progressively decreased with time, 90% of circulating iPSC-RBCs were enucleated 1 day after transfusion (CD235a+ CD233+ CD49d− CD71−). Surprisingly, human iPSC-RBCs reappeared in the peripheral circulation at 3 weeks after transfusion at levels more than 8-fold higher than at 1 h after transfusion. Moreover, a substantial portion of the transfused nucleated iPSC-RBCs preferentially homed to the bone marrow, and were detectable at 24 days after transfusion. These results suggest that nucleated human iPSC-derived cells that homed to the bone marrow of NSG mice retained the capability to complete differentiation into enucleated erythrocytes and egress the bone marrow into peripheral blood. The results offer a new model using human peripheral blood-derived iPSC and CL/CVF-treated NSG mice to investigate the development and circulation of human erythroid cells in vivo.
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影响因子：
82.9
作者：
通讯作者：
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补体消耗改善免疫缺陷小鼠的人红细胞重建
影响因子：
5.9
作者：
Chen, Bing;Fan, Wei;Yang, Yong-Guang
通讯作者：
Yang, Yong-Guang
影响因子：
14.8
作者：
通讯作者：
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影响因子：
7.5
作者：
Heshusius, Steven;Heideveld, Esther;van den Akker, Emile
通讯作者：
van den Akker, Emile
影响因子：
10.1
作者：
Chonat S;Graciaa S;Shin HS;Newton JG;Quarmyne MO;Boudreaux J;Tang A;Zerra PE;Rollins MR;Josephson CD;Brown C;Joiner CH;Fasano RM;Stowell SR
通讯作者：
Stowell SR