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Highly efficient platelet generation in lung vasculature reproduced by microfluidics.
Zhao, Xiaojuan; Alibhai, Dominic; Walsh, Tony G; Tarassova, Nathalie; Englert, Maximilian; Birol, Semra Z; Li, Yong; Williams, Christopher M; Neal, Chris R; Burkard, Philipp; Cross, Stephen J; Aitken, Elizabeth W; Waller, Amie K; Beltrán, José Ballester; Gunning, Peter W; Hardeman, Edna C; Agbani, Ejaife O; Nieswandt, Bernhard; Hers, Ingeborg; Ghevaert, Cedric; Poole, Alastair W.
Afiliação
  • Zhao X; School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK. xz14926@bristol.ac.uk.
  • Alibhai D; Wolfson BioimagingFacility, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
  • Walsh TG; School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
  • Tarassova N; School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
  • Englert M; University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, D-97080, Germany.
  • Birol SZ; School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
  • Li Y; School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
  • Williams CM; School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
  • Neal CR; Wolfson BioimagingFacility, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
  • Burkard P; University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, D-97080, Germany.
  • Cross SJ; Wolfson BioimagingFacility, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
  • Aitken EW; School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
  • Waller AK; University of Cambridge / NHS Blood and Transplant, Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AW, UK.
  • Beltrán JB; University of Cambridge / NHS Blood and Transplant, Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AW, UK.
  • Gunning PW; School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
  • Hardeman EC; School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
  • Agbani EO; Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 1N4, Canada.
  • Nieswandt B; University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, D-97080, Germany.
  • Hers I; School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
  • Ghevaert C; University of Cambridge / NHS Blood and Transplant, Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AW, UK.
  • Poole AW; School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK. A.Poole@bristol.ac.uk.
Nat Commun ; 14(1): 4026, 2023 07 07.
Article em En | MEDLINE | ID: mdl-37419900
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plaquetas / Microfluídica Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plaquetas / Microfluídica Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article