Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation.
Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation.
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DOI：
10.1016/j.stemcr.2018.08.015
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发表时间：
2018-10-09
影响因子：
5.9
通讯作者：
Nakauchi H
中科院分区：
文献类型：
--
作者：
Hamanaka S;Umino A;Sato H;Hayama T;Yanagida A;Mizuno N;Kobayashi T;Kasai M;Suchy FP;Yamazaki S;Masaki H;Yamaguchi T;Nakauchi H
在伴随血管吻合的器官移植的情况下，主要组织相容性复合物不匹配的血管内皮细胞成为移植物排斥的靶。因此，产生无排斥反应的可移植器官需要在器官内同时产生血管内皮细胞。为了产生多能干细胞（PSC）衍生的血管内皮细胞，我们进行了囊胚与血管内皮生长因子受体-2纯合突变囊胚互补。由于内皮细胞和造血细胞的早期缺陷，这种突变在胚胎（E）8.5-9.5天是胚胎致死的。Flk-1基因敲除纯合嵌合小鼠存活至成年1年以上，无任何异常，所有血管内皮细胞和造血细胞均来源于注射的PSC。这种方法可以与诱导器官缺陷的其他基因敲除结合使用，以产生无排斥的可移植器官，其中所有器官的细胞和脉管系统都是PSC衍生的。Flk-1缺陷型PSC对嵌合体小鼠血管内皮细胞无贡献Flk-1缺陷型小鼠通过囊胚互补存活至成年PSC可产生血管内皮细胞和造血细胞本文中，Yamaguchi等通过囊胚互补技术在体内从多能干细胞中产生血管内皮细胞和造血细胞。这种方法可用于产生无排斥反应的可移植器官，其中所有器官的细胞和脉管系统都是多能干细胞衍生的。
In the case of organ transplantation accompanied by vascular anastomosis, major histocompatibility complex mismatched vascular endothelial cells become a target for graft rejection. Production of a rejection-free, transplantable organ, therefore, requires simultaneous generation of vascular endothelial cells within the organ. To generate pluripotent stem cell (PSC)-derived vascular endothelial cells, we performed blastocyst complementation with a vascular endothelial growth factor receptor-2 homozygous mutant blastocyst. This mutation is embryonic lethal at embryonic (E) day 8.5–9.5 due to an early defect in endothelial and hematopoietic cells. The Flk-1 homozygous knockout chimeric mice survived to adulthood for over 1 year without any abnormality, and all vascular endothelial cells and hematopoietic cells were derived from the injected PSCs. This approach could be used in conjunction with other gene knockouts which induce organ deficiency to produce a rejection-free, transplantable organ in which all the organ's cells and vasculature are PSC derived. Flk-1-deficient PSCs did not contribute to vascular endothelial cells in chimeric mice Flk-1-deficient mice survived into adulthood by blastocyst complementation Both vascular endothelial cells and hematopoietic cells were generated from PSCs In this article, Yamaguchi and colleagues generated vascular endothelial cells and hematopoietic cells from pluripotent stem cells in vivo by blastocyst complementation technique. This approach could be used to produce a rejection-free, transplantable organ in which all the organ's cells and vasculature are pluripotent stem cell derived.
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DOI：
10.1084/jem.20120340
发表时间：
2012-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hoeffel G;Wang Y;Greter M;See P;Teo P;Malleret B;Leboeuf M;Low D;Oller G;Almeida F;Choy SH;Grisotto M;Renia L;Conway SJ;Stanley ER;Chan JK;Ng LG;Samokhvalov IM;Merad M;Ginhoux F
通讯作者：
Ginhoux F
影响因子：
5.9
作者：
Assawachananont, Juthaporn;Mandai, Michiko;Okamoto, Satoshi;Yamada, Chikako;Eiraku, Mototsugu;Yonemura, Shigenobu;Sasai, Yoshiki;Takahashi, Masayo
通讯作者：
Takahashi, Masayo
影响因子：
64.5
作者：
Shalaby, F;Ho, J;Rossant, J
通讯作者：
Rossant, J
影响因子：
20.1
作者：
Nakamura, Tomoki;Colbert, Melissa C.;Robbins, Jeffrey
通讯作者：
Robbins, Jeffrey
影响因子：
3.7
作者：
Hamanaka S;Yamaguchi T;Kobayashi T;Kato-Itoh M;Yamazaki S;Sato H;Umino A;Wakiyama Y;Arai M;Sanbo M;Hirabayashi M;Nakauchi H
通讯作者：
Nakauchi H