Scalable generation of universal platelets from human induced pluripotent stem cells.
Scalable generation of universal platelets from human induced pluripotent stem cells.
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DOI：
10.1016/j.stemcr.2014.09.010
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发表时间：
2014-11-11
影响因子：
5.9
通讯作者：
Lanza, Robert
中科院分区：
文献类型：
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作者：
Feng, Qiang;Shabrani, Namrata;Thon, Jonathan N.;Huo, Hongguang;Thiel, Austin;Machlus, Kellie R.;Kim, Kyungho;Brooks, Julie;Li, Feng;Luo, Chenmei;Kimbrel, Erin A.;Wang, Jiwu;Kim, Kwang-Soo;Italiano, Joseph;Cho, Jaehyung;Lu, Shi-Jiang;Lanza, Robert
人诱导多能干细胞(IPSCs)为生产可输血的血小板提供了一种潜在的可补充来源。在此，我们描述了一种在无血清/饲养层条件下从IPSCs以可扩展的方式生成巨核细胞(MK)和功能血小板的方法。该方法还允许对MK祖细胞进行冷冻保存，当需要大量血小板时，能够实现快速的“激增”能力。超微结构/形态分析表明，IPSC血小板与人血血小板没有显著差异。IPSC血小板在激活后形成聚集体、片状脂膜和丝状足，在巨噬细胞耗竭的动物体内循环，并以与人类血小板相同的方式并入正在形成的小鼠血栓中。通过敲除β2-微球蛋白基因，我们产生了主要组织相容性抗原阴性的血小板。从可再生细胞来源中可扩展地生成人类白细胞抗原ABC阴性的血小板，代表着朝着生成用于输血的通用血小板迈出的重要一步，也是治疗血小板难治性的一种潜在策略。在特定条件下从人IPSCs大规模生产血小板IPSC在体内和体外都具有功能-IPSCs中β2微球蛋白基因的敲除产生通用血小板兰扎和他的同事报告了一种以可扩展的方式从人IPSCs产生功能血小板的方法。IPSC血小板在激活后形成聚集体、片状脂膜和丝状伪足，在动物体内循环，并以与人类血小板相同的方式并入正在形成的血栓中。此外，还从IPSCs中产生了HLA-ABC阴性的血小板，这代表了为临床输血而产生通用血小板的第一步。
Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid “surge” capacity when large numbers of platelets are needed. Ultrastructural/morphological analyses show no major differences between iPSC platelets and human blood platelets. iPSC platelets form aggregates, lamellipodia, and filopodia after activation and circulate in macrophage-depleted animals and incorporate into developing mouse thrombi in a manner identical to human platelets. By knocking out the β2-microglobulin gene, we have generated platelets that are negative for the major histocompatibility antigens. The scalable generation of HLA-ABC-negative platelets from a renewable cell source represents an important step toward generating universal platelets for transfusion as well as a potential strategy for the management of platelet refractoriness. Large-scale production of platelets from human iPSCs under defined conditions iPSC platelets are functional both in vivo and in vitro Knockout of β2-microglobulin gene in iPSCs generates universal platelets Lanza and colleagues report a method to generate functional platelets from human iPSCs in a scalable manner. iPSC platelets formed aggregates, lamellipodia, and filopodia after activation and circulated in animals and incorporated into developing thrombi in a manner identical to human platelets. HLA-ABC-negative platelets were also generated from iPSCs, which represents the first step toward generating universal platelets for clinical transfusion.
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影响因子：
15.9
作者：
DURSO, CM;WANG, ZG;FERRONE, S
通讯作者：
FERRONE, S
DOI：
10.1182/blood.v26.6.720.720
发表时间：
1965-01-01
期刊：
BLOOD-THE JOURNAL OF HEMATOLOGY
影响因子：
--
作者：
KAUFMAN, RM;AIRO, R;CROSBY, WH
通讯作者：
CROSBY, WH
影响因子：
20.3
作者：
Hu, Zheng;Yang, Yong-Guang
通讯作者：
Yang, Yong-Guang
金属蛋白酶调节可改善小鼠胚胎干细胞的体外产生有效的血小板。
影响因子：
15.3
作者：
Nishikii, Hidekazu;Eto, Koji;Tamura, Noriko;Hattori, Koichi;Heissig, Beate;Kanaji, Taisuke;Sawaguchi, Akira;Goto, Shinya;Ware, Jerry;Nakauchi, Hiromitsu
通讯作者：
Nakauchi, Hiromitsu
影响因子：
44.1
作者：
通讯作者：
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