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Highly efficient platelet generation in lung vasculature reproduced by microfluidics

Published version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Tarassova, Nathalie 
Englert, Maximilian  ORCID logo  https://orcid.org/0000-0002-9066-5801

Abstract

jats:titleAbstract</jats:title>jats:pPlatelets, small hemostatic blood cells, are derived from megakaryocytes. Both bone marrow and lung are principal sites of thrombopoiesis although underlying mechanisms remain unclear. Outside the body, however, our ability to generate large number of functional platelets is poor. Here we show that perfusion of megakaryocytes ex vivo through the mouse lung vasculature generates substantial platelet numbers, up to 3000 per megakaryocyte. Despite their large size, megakaryocytes are able repeatedly to passage through the lung vasculature, leading to enucleation and subsequent platelet generation intravascularly. Using ex vivo lung and an in vitro microfluidic chamber we determine how oxygenation, ventilation, healthy pulmonary endothelium and the microvascular structure support thrombopoiesis. We also show a critical role for the actin regulator Tropomyosin 4 in the final steps of platelet formation in lung vasculature. This work reveals the mechanisms of thrombopoiesis in lung vasculature and informs approaches to large-scale generation of platelets.</jats:p>

Description

Keywords

Mice, Animals, Blood Platelets, Microfluidics, Megakaryocytes, Thrombopoiesis, Lung

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

14

Publisher

Nature Portfolio
Sponsorship
Wellcome Trust (219472/A/19/Z)
Wellcome Trust (219472/Z/19/Z)