Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice.
Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice.
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作者：
血小板在止血和动脉粥样硬化血栓形成中发挥重要作用。由于储存时间短，对这种救命血液成分的需求不断增加。在这项研究中，我们报告说，从人胚胎干细胞（hESC）中大规模产生功能性巨核细胞和血小板是可行的。微分干涉对比和电子显微镜分析表明，hESC 来源的血小板的超微结构和形态学特征与正常血小板没有区别。在功能测定中，hESC 衍生的血小板对凝血酶刺激作出反应，形成微聚集体，并促进体外凝块形成/收缩。活细胞显微镜检查表明，hESC 血小板响应凝血酶激活而形成片状伪足和丝状伪足，并且如在正常血液中观察到的那样相互束缚。使用实时活体成像和高速视频显微镜，我们还表明，hESC 衍生的血小板有助于在小鼠激光诱导的血管损伤部位形成血栓，这为 hESC 衍生的血小板的体内功能提供了第一个证据。这些结果代表了向无限供应输血用血小板迈出的重要一步。由于血小板不含遗传物质，因此它们是涉及人类多能干细胞的早期临床转化的理想候选者。
Platelets play an essential role in hemostasis and atherothrombosis. Owing to their short storage time, there is constant demand for this life-saving blood component. In this study, we report that it is feasible to generate functional megakaryocytes and platelets from human embryonic stem cells (hESCs) on a large scale. Differential-interference contrast and electron microscopy analyses showed that ultrastructural and morphological features of hESC-derived platelets were indistinguishable from those of normal blood platelets. In functional assays, hESC-derived platelets responded to thrombin stimulation, formed microaggregates, and facilitated clot formation/retraction in vitro. Live cell microscopy demonstrated that hESC-platelets formed lamellipodia and filopodia in response to thrombin activation, and tethered to each other as observed in normal blood. Using real-time intravital imaging with high-speed video microscopy, we have also shown that hESC-derived platelets contribute to developing thrombi at sites of laser-induced vascular injury in mice, providing the first evidence for in vivo functionality of hESC-derived platelets. These results represent an important step toward generating an unlimited supply of platelets for transfusion. Since platelets contain no genetic material, they are ideal candidates for early clinical translation involving human pluripotent stem cells.
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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：
2.1
作者：
Kosaki, G
通讯作者：
Kosaki, G
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：
23.9
作者：
Kim D;Kim CH;Moon JI;Chung YG;Chang MY;Han BS;Ko S;Yang E;Cha KY;Lanza R;Kim KS
通讯作者：
Kim KS
影响因子：
82.9
作者：
Falati, S;Gross, P;Furie, B
通讯作者：
Furie, B