title: Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice.
abstract: 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.
authors.affiliation: Stem Cell and Regenerative Medicine International, 33 Locke Drive, Marlborough, MA 01752, USA. jlu@steminternational.com
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Yin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.forename: Erin A
authors.initials: EA
authors.lastname: Kimbrel
authors.forename: Eunsil
authors.initials: E
authors.lastname: Hahm
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Thon
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Italiano
authors.forename: Jaehyung
authors.initials: J
authors.lastname: Cho
authors.forename: Robert
authors.initials: R
authors.lastname: Lanza
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D017713:Platelet Transfusion; D011554:Pseudopodia / Q000502:physiology
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex