Abstract
The in vitro production of platelets could provide a life-saving intervention for patients that would otherwise require donor-derived platelets. Producing large numbers of platelets in vitro from their progenitor cells, megakaryocytes, remains remarkably difficult and inefficient. Here, a human megakaryoblast leukemia cell line (MEG-01) was used to assess the maturation of megakaryocytes and to develop a new methodology for producing high numbers of platelet-like particles from mature MEG-01 cells in vitro.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Chang Y, Bluteau D, Debili N et al (2007) From hematopoietic stem cells to platelets. J Thromb Haemost 5(Suppl 1):318–327. https://doi.org/10.1111/j.1538-7836.2007.02472.x
Deutsch VR, Tomer A (2006) Megakaryocyte development and platelet production. Br J Haematol 134(5):453–466. https://doi.org/10.1111/j.1365-2141.2006.06215.x
Machlus KR, Italiano JE Jr (2013) The incredible journey: From megakaryocyte development to platelet formation. J Cell Biol 201(6):785–796. https://doi.org/10.1083/jcb.201304054
Machlus KR, Thon JN, Italiano JE Jr (2014) Interpreting the developmental dance of the megakaryocyte: a review of the cellular and molecular processes mediating platelet formation. Br J Haematol 165(2):227–236. https://doi.org/10.1111/bjh.12758
Brown E, Carlin LM, Nerlov C et al (2018) Multiple membrane extrusion sites drive megakaryocyte migration into bone marrow blood vessels. Life Sci Alliance 1(2):e201800061. https://doi.org/10.26508/lsa.201800061
Harker LA, Finch CA (1969) Thrombokinetics in man. J Clin Invest 48(6):963–974. https://doi.org/10.1172/JCI106077
Lambert MP, Sullivan SK, Fuentes R et al (2013) Challenges and promises for the development of donor-independent platelet transfusions. Blood 121(17):3319–3324. https://doi.org/10.1182/blood-2012-09-455428
Ogura M, Morishima Y, Ohno R et al (1985) Establishment of a novel human megakaryoblastic leukemia cell line, MEG-01, with positive Philadelphia chromosome. Blood 66(6):1384–1392
Risitano A, Beaulieu LM, Vitseva O et al (2012) Platelets and platelet-like particles mediate intercellular RNA transfer. Blood 119(26):6288–6295. https://doi.org/10.1182/blood-2011-12-396440
Takeuchi K, Satoh M, Kuno H et al (1998) Platelet-like particle formation in the human megakaryoblastic leukaemia cell lines, MEG-01 and MEG-01s. Br J Haematol 100(2):436–444. https://doi.org/10.1046/j.1365-2141.1998.00576.x
Bernard JJ, Seweryniak KE, Koniski AD et al (2009) Foxp3 regulates megakaryopoiesis and platelet function. Arterioscler Thromb Vasc Biol 29(11):1874–1882. https://doi.org/10.1161/ATVBAHA.109.193805
Greenberg SM, Rosenthal DS, Greeley TA et al (1988) Characterization of a new megakaryocytic cell line: the Dami cell. Blood 72(6):1968–1977
Nagano T, Ohga S, Kishimoto Y et al (1992) Ultrastructural analysis of platelet-like particles from a human megakaryocytic leukemia cell line (CMK 11-5). Int J Hematol 56(1):67–78
Sledge GW Jr, Glant M, Jansen J et al (1986) Establishment in long term culture of megakaryocytic leukemia cells (EST-IU) from the marrow of a patient with leukemia and a mediastinal germ cell neoplasm. Cancer Res 46(4 Pt 2):2155–2159
Takeuchi K, Ogura M, Saito H et al (1991) Production of platelet-like particles by a human megakaryoblastic leukemia cell line (MEG-01). Exp Cell Res 193(1):223–226. https://doi.org/10.1016/0014-4827(91)90560-h
Tange T, Takei Y, Takaai S et al (1988) In-vitro production of human platelets. Lancet 2(8604):218. https://doi.org/10.1016/s0140-6736(88)92318-5
Yang XL, Ge MK, Mao DK et al (2016) Thrombin maybe plays an important role in MK differentiation into platelets. Biomed Res Int 2016:9313269. https://doi.org/10.1155/2016/9313269
Isakari Y, Sogo S, Ishida T et al (2009) Gene expression analysis during platelet-like particle production in phorbol myristate acetate-treated MEG-01 cells. Biol Pharm Bull 32(3):354–358. https://doi.org/10.1248/bpb.32.354
Battinelli E, Willoughby SR, Foxall T et al (2001) Induction of platelet formation from megakaryocytoid cells by nitric oxide. Proc Natl Acad Sci U S A 98(25):14458–14463. https://doi.org/10.1073/pnas.241427398
Acknowledgments
The authors gratefully acknowledge the funding sources to support this work from the National Science Foundation CAREER Program (CBET-1554017), the Office of Naval Research Young Investigator Program (N00014-16-1-3012), the National Institutes of Health Trailblazer Award (1R21EB025413-01), the National Institutes of Health Director’s New Innovator Award (1DP2CA250006-01), and the Undergraduate Research Opportunity Program (awarded to KP and ML). This work was also supported by the University of Utah Flow Cytometry Facility, the University of Utah Fluorescence Microscopy Core Facility (1S10RR024761-01), the National Cancer Institute (5P30CA042014-24), and the National Center for Research of the National Institutes of Health (1S10RR026802-01).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Persson, K.M., Kneller, P.V., Livingston, M.W., Bush, L.M., Deans, T.L. (2021). High-Throughput Production of Platelet-Like Particles. In: Ebrahimkhani, M.R., Hislop, J. (eds) Programmed Morphogenesis. Methods in Molecular Biology, vol 2258. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1174-6_18
Download citation
DOI: https://doi.org/10.1007/978-1-0716-1174-6_18
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1173-9
Online ISBN: 978-1-0716-1174-6
eBook Packages: Springer Protocols