Highly efficient platelet generation in lung vasculature reproduced by microfluidics

Xiaojuan Zhao (), Dominic Alibhai, Tony G. Walsh, Nathalie Tarassova, Maximilian Englert, Semra Z. Birol, Yong Li, Christopher M. Williams, Chris R. Neal, Philipp Burkard, Stephen J. Cross, Elizabeth W. Aitken, Amie K. Waller, José Ballester Beltrán, Peter W. Gunning, Edna C. Hardeman, Ejaife O. Agbani, Bernhard Nieswandt, Ingeborg Hers, Cedric Ghevaert and Alastair W. Poole ()
Additional contact information
Xiaojuan Zhao: University of Bristol
Dominic Alibhai: University of Bristol
Tony G. Walsh: University of Bristol
Nathalie Tarassova: University of Bristol
Maximilian Englert: University of Würzburg
Semra Z. Birol: University of Bristol
Yong Li: University of Bristol
Christopher M. Williams: University of Bristol
Chris R. Neal: University of Bristol
Philipp Burkard: University of Würzburg
Stephen J. Cross: University of Bristol
Elizabeth W. Aitken: University of Bristol
Amie K. Waller: University of Cambridge / NHS Blood and Transplant, Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge
José Ballester Beltrán: University of Cambridge / NHS Blood and Transplant, Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge
Peter W. Gunning: University of New South Wales
Edna C. Hardeman: University of New South Wales
Ejaife O. Agbani: University of Calgary
Bernhard Nieswandt: University of Würzburg
Ingeborg Hers: University of Bristol
Cedric Ghevaert: University of Cambridge / NHS Blood and Transplant, Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge
Alastair W. Poole: University of Bristol

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Platelets, 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.

Date: 2023
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39598-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39598-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39598-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().