Shear Enhances Thrombopoiesis and Formation of Microparticles That Induce Megakaryocytic Differentiation of Stem Cells

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2014 Jun 21

PMID 24948658

Citations 37

Authors

Jinlin Jiang

Donna S Woulfe

Eleftherios T Papoutsakis

Affiliations

Soon will be listed here.

Abstract

In vivo visualization of thrombopoiesis suggests an important role for shear flow in platelet biogenesis. In vitro, shear stress was shown to accelerate proplatelet formation from mature megakaryocytes (Mks). Yet, the role of biomechanical forces on Mk biology and platelet biogenesis remains largely unexplored. In this study, we investigated the impact of shear stress on Mk maturation and formation of platelet-like particles (PLPs), pro/preplatelets (PPTs), and Mk microparticles (MkMPs), and furthermore, we explored a physiological role for MkMPs. We found that shear accelerated DNA synthesis of immature Mks in an exposure time- and shear stress level-dependent manner. Both phosphatidylserine exposure and caspase-3 activation were enhanced by shear stress. Exposure to physiological shear dramatically increased generation of PLPs/PPTs and MkMPs by up to 10.8 and 47-fold, respectively. Caspase-3 inhibition reduced shear-induced PLP/PPT and MkMP formation. PLPs generated under shear flow displayed improved functionality as assessed by CD62P exposure and fibrinogen binding. Significantly, coculture of MkMPs with hematopoietic stem and progenitor cells promoted hematopoietic stem and progenitor cell differentiation to mature Mks synthesizing α- and dense-granules, and forming PPTs without exogenous thrombopoietin, thus identifying a novel and unexplored potential physiological role for MkMPs.

Citing Articles

Engineered and hybrid human megakaryocytic extracellular vesicles for targeted non-viral cargo delivery to hematopoietic (blood) stem and progenitor cells.

Das S, Thompson W, Papoutsakis E Front Bioeng Biotechnol. 2024; 12:1435228.

PMID: 39386042 PMC: 11461334. DOI: 10.3389/fbioe.2024.1435228.

Physical modulation of mesenchymal stem cell exosomes: A new perspective for regenerative medicine.

Wu D, Zhao X, Xie J, Yuan R, Li Y, Yang Q Cell Prolif. 2024; 57(8):e13630.

PMID: 38462759 PMC: 11294442. DOI: 10.1111/cpr.13630.

Thompson W, Papoutsakis E Bioeng Transl Med. 2023; 8(5):e10563.

PMID: 37693047 PMC: 10486331. DOI: 10.1002/btm2.10563.

Megakaryocyte membrane-wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells.

Das S, Harris J, Winter E, Kao C, Day E, Papoutsakis E Bioeng Transl Med. 2023; 8(3):e10456.

PMID: 37206243 PMC: 10189472. DOI: 10.1002/btm2.10456.

Extracellular vesicle-mediated remodeling of the bone marrow microenvironment in myeloid malignancies.

Hayashi Y, Nishimura K, Tanaka A, Inoue D Int J Hematol. 2023; 117(6):821-829.

PMID: 37041345 DOI: 10.1007/s12185-023-03587-x.

References

Wang J, Jen C, Kung H, Lin L, Hsiue T, Chen H . Different effects of strenuous exercise and moderate exercise on platelet function in men. Circulation. 1994; 90(6):2877-85. DOI: 10.1161/01.cir.90.6.2877. View

Abid Hussein M, Nieuwland R, Hau C, Evers L, Meesters E, Sturk A . Cell-derived microparticles contain caspase 3 in vitro and in vivo. J Thromb Haemost. 2005; 3(5):888-96. DOI: 10.1111/j.1538-7836.2005.01240.x. View

Leytin V . Apoptosis in the anucleate platelet. Blood Rev. 2011; 26(2):51-63. DOI: 10.1016/j.blre.2011.10.002. View

Sapet C, Simoncini S, Loriod B, Puthier D, Sampol J, Nguyen C . Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2. Blood. 2006; 108(6):1868-76. DOI: 10.1182/blood-2006-04-014175. View

Hattori K, Heissig B, Rafii S . The regulation of hematopoietic stem cell and progenitor mobilization by chemokine SDF-1. Leuk Lymphoma. 2003; 44(4):575-82. DOI: 10.1080/1042819021000037985. View

Reininger A, Heijnen H, Schumann H, Specht H, Schramm W, Ruggeri Z . Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress. Blood. 2006; 107(9):3537-45. PMC: 1895770. DOI: 10.1182/blood-2005-02-0618. View

Chen C, Fuhrken P, Huang L, Apostolidis P, Wang M, Paredes C . A systems-biology analysis of isogenic megakaryocytic and granulocytic cultures identifies new molecular components of megakaryocytic apoptosis. BMC Genomics. 2007; 8:384. PMC: 2204013. DOI: 10.1186/1471-2164-8-384. View

Schulze H, Shivdasani R . Mechanisms of thrombopoiesis. J Thromb Haemost. 2005; 3(8):1717-24. DOI: 10.1111/j.1538-7836.2005.01426.x. View

Fuhrken P, Apostolidis P, Lindsey S, Miller W, Papoutsakis E . Tumor suppressor protein p53 regulates megakaryocytic polyploidization and apoptosis. J Biol Chem. 2008; 283(23):15589-600. PMC: 2414295. DOI: 10.1074/jbc.M801923200. View

10.

Yamamoto K, Takahashi T, Asahara T, Ohura N, Sokabe T, Kamiya A . Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress. J Appl Physiol (1985). 2003; 95(5):2081-8. DOI: 10.1152/japplphysiol.00232.2003. View

11.

Martinez M, Larbret F, Zobairi F, Coulombe J, Debili N, Vainchenker W . Transfer of differentiation signal by membrane microvesicles harboring hedgehog morphogens. Blood. 2006; 108(9):3012-20. DOI: 10.1182/blood-2006-04-019109. View

12.

Morison I, Cramer Borde E, Cheesman E, Cheong P, Holyoake A, Fichelson S . A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia. Nat Genet. 2008; 40(4):387-9. DOI: 10.1038/ng.103. View

13.

Rosado J, Lopez J, Gomez-Arteta E, Redondo P, Salido G, Pariente J . Early caspase-3 activation independent of apoptosis is required for cellular function. J Cell Physiol. 2006; 209(1):142-52. DOI: 10.1002/jcp.20715. View

14.

Palumbo R, Gaetano C, Melillo G, Toschi E, Remuzzi A, Capogrossi M . Shear stress downregulation of platelet-derived growth factor receptor-beta and matrix metalloprotease-2 is associated with inhibition of smooth muscle cell invasion and migration. Circulation. 2000; 102(2):225-30. DOI: 10.1161/01.cir.102.2.225. View

15.

Ye C, Bai L, Yan Z, Wang Y, Jiang Z . Shear stress and vascular smooth muscle cells promote endothelial differentiation of endothelial progenitor cells via activation of Akt. Clin Biomech (Bristol). 2007; 23 Suppl 1:S118-24. DOI: 10.1016/j.clinbiomech.2007.08.018. View

16.

Mostafa S, Miller W, Papoutsakis E . Oxygen tension influences the differentiation, maturation and apoptosis of human megakaryocytes. Br J Haematol. 2000; 111(3):879-89. View

17.

Metallo C, Vodyanik M, de Pablo J, Slukvin I, Palecek S . The response of human embryonic stem cell-derived endothelial cells to shear stress. Biotechnol Bioeng. 2008; 100(4):830-7. DOI: 10.1002/bit.21809. View

18.

Ismail N, Wang Y, Dakhlallah D, Moldovan L, Agarwal K, Batte K . Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood. 2012; 121(6):984-95. PMC: 3567345. DOI: 10.1182/blood-2011-08-374793. View

19.

Clarke M, Savill J, Jones D, Noble B, Brown S . Compartmentalized megakaryocyte death generates functional platelets committed to caspase-independent death. J Cell Biol. 2003; 160(4):577-87. PMC: 2173731. DOI: 10.1083/jcb.200210111. View

20.

Quesenberry P, Dooner M, Aliotta J . Stem cell plasticity revisited: the continuum marrow model and phenotypic changes mediated by microvesicles. Exp Hematol. 2010; 38(7):581-92. PMC: 2887723. DOI: 10.1016/j.exphem.2010.03.021. View