Review
Ex Vivo production of platelets from stem cells
Mauro P. Avanzi,
William Beau Mitchell,
Corresponding Author
Mauro P. Avanzi
Platelet Biology Laboratory, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY, USA
Correspondence: Dr Mauro P. Avanzi, Platelet Biology Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street, New York, NY 10065, USA.
E-mail: [email protected]
Search for more papers by this authorWilliam Beau Mitchell
Platelet Biology Laboratory, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY, USA
Search for more papers by this authorMauro P. Avanzi,
William Beau Mitchell,
Corresponding Author
Mauro P. Avanzi
Platelet Biology Laboratory, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY, USA
Correspondence: Dr Mauro P. Avanzi, Platelet Biology Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street, New York, NY 10065, USA.
E-mail: [email protected]
Search for more papers by this authorWilliam Beau Mitchell
Platelet Biology Laboratory, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY, USA
Search for more papers by this authorSummary
Stem cell technology holds great promise for transfusion medicine, and generation of platelets from stem cells would be transformative. Platelet transfusions are life saving for millions of people and the clinical demand for platelets continues to increase: there is a real need to increase the supply of platelets. Accordingly, there is great interest in the potential of producing platelets from stem cells for clinical use. There has been initial success in ex vivo generation of platelets from stem cells using cord blood stem cells, embryonic stem cells and induced pluripotent stem cells. However, the platelet yields achieved by these strategies have not been sufficient for clinical purposes. This review provides updated information about the current strategies of ex vivo generation of platelets. Megakaryocytopoiesis and platelet generation, along with the importance of genetic determinants of these processes, are reviewed in the context of efforts to generate these products from stem cells. Current challenges and rate-limiting steps in ex vivo platelet generation are discussed, together with strategies to overcome them. While much work remains, great progress has been made, moving ex vivo generation of platelets ever closer to the clinic.
References
- Addis, R.C. & Epstein, J.A. (2013) Induced regeneration–the progress and promise of direct reprogramming for heart repair. Nature Medicine, 19, 829–836.
- Avanzi, M.P., Chen, A., He, W. & Mitchell, W.B. (2012) Optimizing megakaryocyte polyploidization by targeting multiple pathways of cytokinesis. Transfusion, 52, 2406–2413.
- Avanzi, M.P., Goldberg, F., Davila, J., Langhi, D., Chiattone, C. & Mitchell, W.B. (2014) Rho kinase inhibition drives megakaryocyte polyploidization and proplatelet formation through MYC and NFE2 downregulation. British Journal of Haematology, doi: 10.1111/bjh.12709
- Avecilla, S.T., Hattori, K., Heissig, B., Tejada, R., Liao, F., Shido, K., Jin, D.K., Dias, S., Zhang, F., Hartman, T.E., Hackett, N.R., Crystal, R.G., Witte, L., Hicklin, D.J., Bohlen, P., Eaton, D., Lyden, D., de Sauvage, F. & Rafii, S. (2004) Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nature Medicine, 10, 64–71.
- Balduini, A., Pallotta, I., Malara, A., Lova, P., Pecci, A., Viarengo, G., Balduini, C.L. & Torti, M. (2008) Adhesive receptors, extracellular proteins and myosin IIA orchestrate proplatelet formation by human megakaryocytes. Jornal of Thrombosis and Haemostasis, 6, 1900–1907.
- Balduini, A., Malara, A., Balduini, C.L. & Noris, P. (2011) Megakaryocytes derived from patients with the classical form of Bernard-Soulier syndrome show no ability to extend proplatelets in vitro. Platelets, 22, 308–311.
- Balduini, A., Di Buduo, C.A., Malara, A., Lecchi, A., Rebuzzini, P., Currao, M., Pallotta, I., Jakubowski, J.A. & Cattaneo, M. (2012) Constitutively released adenosine diphosphate regulates proplatelet formation by human megakaryocytes. Haematologica, 97, 1657–1665.
- Barr, F.A. & Gruneberg, U. (2007) Cytokinesis: placing and making the final cut. Cell, 131, 847–860.
- Bartsch, T., Brehm, M., Zeus, T., Kogler, G., Wernet, P. & Strauer, B.E. (2007) Transplantation of autologous mononuclear bone marrow stem cells in patients with peripheral arterial disease (the TAM-PAD study). Clin Res Cardiol, 96, 891–899.
- Battinelli, E., Willoughby, S.R., Foxall, T., Valeri, C.R. & Loscalzo, J. (2001) Induction of platelet formation from megakaryocytoid cells by nitric oxide. Proceedings of the National Academy of Sciences of the United States of America, 98, 14458–14463.
- Bergmeier, W., Burger, P.C., Piffath, C.L., Hoffmeister, K.M., Hartwig, J.H., Nieswandt, B. & Wagner, D.D. (2003) Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse platelets. Blood, 102, 4229–4235.
- Bertolini, F., Battaglia, M., Pedrazzoli, P., Da Prada, G.A., Lanza, A., Soligo, D., Caneva, L., Sarina, B., Murphy, S., Thomas, T. & della Cuna, G.R. (1997) Megakaryocytic progenitors can be generated ex vivo and safely administered to autologous peripheral blood progenitor cell transplant recipients. Blood, 89, 2679–2688.
- Bertozzi, C.C., Hess, P.R. & Kahn, M.L. (2010) Platelets: covert regulators of lymphatic development. Arteriosclerosis, Thrombosis, and Vascular Biology, 30, 2368–2371.
- Bluteau, D., Lordier, L., Di Stefano, A., Chang, Y., Raslova, H., Debili, N. & Vainchenker, W. (2009) Regulation of megakaryocyte maturation and platelet formation. Jornal of Thrombosis and Haemostasis, 7, 227–234.
- Boitano, A.E., Wang, J., Romeo, R., Bouchez, L.C., Parker, A.E., Sutton, S.E., Walker, J.R., Flaveny, C.A., Perdew, G.H., Denison, M.S., Schultz, P.G. & Cooke, M.P. (2010) Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science, 329, 1345–1348.
- Bringmann, H. (2005) Cytokinesis and the spindle midzone. Cell Cycle, 4, 1709–1712.
- Chanprasert, S., Geddis, A.E., Barroga, C., Fox, N.E. & Kaushansky, K. (2006) Thrombopoietin (TPO) induces c-myc expression through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKCzeta or mTOR in TPO-dependent cell lines and primary megakaryocytes. Cellular Signalling, 18, 1212–1218.
- Chen, J., Tan, K., Zhou, H., Lo, H.F., Roux, D.T., Liddington, R.C. & Diacovo, T.G. (2008) Modifying murine von Willebrand factor A1 domain for in vivo assessment of human platelet therapies. Nature Biotechnology, 26, 114–119.
- Choi, E.S., Nichol, J.L., Hokom, M.M., Hornkohl, A.C. & Hunt, P. (1995) Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional. Blood, 85, 402–413.
- Clarke, M.C., Savill, J., Jones, D.B., Noble, B.S. & Brown, S.B. (2003) Compartmentalized megakaryocyte death generates functional platelets committed to caspase-independent death. Journal of Cell Biology, 160, 577–587.
- Cortin, V., Garnier, A., Pineault, N., Lemieux, R., Boyer, L. & Proulx, C. (2005) Efficient in vitro megakaryocyte maturation using cytokine cocktails optimized by statistical experimental design. Experimental Hematology, 33, 1182–1191.
- Currao, M., Balduini, C.L. & Balduini, A. (2013) High doses of romiplostim induce proliferation and reduce proplatelet formation by human megakaryocytes. PLoS ONE, 8, e54723.
- De Botton, S., Sabri, S., Daugas, E., Zermati, Y., Guidotti, J.E., Hermine, O., Kroemer, G., Vainchenker, W. & Debili, N. (2002) Platelet formation is the consequence of caspase activation within megakaryocytes. Blood, 100, 1310–1317.
- Delaney, C., Heimfeld, S., Brashem-Stein, C., Voorhies, H., Manger, R.L. & Bernstein, I.D. (2010) Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nature Medicine, 16, 232–236.
- Deutsch, V.R. & Tomer, A. (2006) Megakaryocyte development and platelet production. British Journal of Haematology, 134, 453–466.
- Deutsch, V.R. & Tomer, A. (2013) Advances in megakaryocytopoiesis and thrombopoiesis: from bench to bedside. British Journal of Haematology, 161, 778–793.
- Dunois-Larde, C., Capron, C., Fichelson, S., Bauer, T., Cramer-Borde, E. & Baruch, D. (2009) Exposure of human megakaryocytes to high shear rates accelerates platelet production. Blood, 114, 1875–1883.
- Elagib, K.E., Racke, F.K., Mogass, M., Khetawat, R., Delehanty, L.L. & Goldfarb, A.N. (2003) RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation. Blood, 101, 4333–4341.
- Ferrer-Marin, F., Liu, Z.J., Gutti, R. & Sola-Visner, M. (2010) Neonatal thrombocytopenia and megakaryocytopoiesis. Seminars in Hematology, 47, 281–288.
- Figueiredo, C., Goudeva, L., Horn, P.A., Eiz-Vesper, B., Blasczyk, R. & Seltsam, A. (2010) Generation of HLA-deficient platelets from hematopoietic progenitor cells. Transfusion, 50, 1690–1701.
- Fuchs, D.A., McGinn, S.G., Cantu, C.L., Klein, R.R., Sola-Visner, M.C. & Rimsza, L.M. (2012) Developmental differences in megakaryocyte size in infants and children. American Journal of Clinical Pathology, 138, 140–145.
- Fuentes, R., Wang, Y., Hirsch, J., Wang, C., Rauova, L., Worthen, G.S., Kowalska, M.A. & Poncz, M. (2010) Infusion of mature megakaryocytes into mice yields functional platelets. Journal of Clinical Investigation, 120, 3917–3922.
- Gadea, G., de Toledo, M., Anguille, C. & Roux, P. (2007) Loss of p53 promotes RhoA-ROCK-dependent cell migration and invasion in 3D matrices. Journal of Cell Biology, 178, 23–30.
- Gaur, M., Kamata, T., Wang, S., Moran, B., Shattil, S.J. & Leavitt, A.D. (2006) Megakaryocytes derived from human embryonic stem cells: a genetically tractable system to study megakaryocytopoiesis and integrin function. Jornal of Thrombosis and Haemostasis, 4, 436–442.
- Gay, L.J. & Felding-Habermann, B. (2011) Contribution of platelets to tumour metastasis. Nature Reviews Cancer, 11, 123–134.
- Geddis, A.E. (2010) Megakaryopoiesis. Seminars in Hematology, 47, 212–219.
- Giammona, L.M., Panuganti, S., Kemper, J.M., Apostolidis, P.A., Lindsey, S., Papoutsakis, E.T. & Miller, W.M. (2009) Mechanistic studies on the effects of nicotinamide on megakaryocytic polyploidization and the roles of NAD+ levels and SIRT inhibition. Experimental Hematology, 37, e1343.
- Guo, Y., Niu, C., Breslin, P., Tang, M., Zhang, S., Wei, W., Kini, A.R., Paner, G.P., Alkan, S., Morris, S.W., Diaz, M., Stiff, P.J. & Zhang, J. (2009) c-Myc-mediated control of cell fate in megakaryocyte-erythrocyte progenitors. Blood, 114, 2097–2106.
- Hanoun, M. & Frenette, P.S. (2013) This niche is a maze; an amazing niche. Cell Stem Cell, 12, 391–392.
- Holme, S., Sweeney, J.D., Sawyer, S. & Elfath, M.D. (1997) The expression of p-selectin during collection, processing, and storage of platelet concentrates: relationship to loss of in vivo viability. Transfusion, 37, 12–17.
- Ichikawa, M., Asai, T., Saito, T., Seo, S., Yamazaki, I., Yamagata, T., Mitani, K., Chiba, S., Ogawa, S., Kurokawa, M. & Hirai, H. (2004) AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nature Medicine, 10, 299–304.
- Josefsson, E.C., James, C., Henley, K.J., Debrincat, M.A., Rogers, K.L., Dowling, M.R., White, M.J., Kruse, E.A., Lane, R.M., Ellis, S., Nurden, P., Mason, K.D., O'Reilly, L.A., Roberts, A.W., Metcalf, D., Huang, D.C. & Kile, B.T. (2011) Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets. Journal of Experimental Medicine, 208, 2017–2031.
- Junt, T., Schulze, H., Chen, Z., Massberg, S., Goerge, T., Krueger, A., Wagner, D.D., Graf, T., Italiano, J.E. Jr, Shivdasani, R.A. & von Andrian, U.H. (2007) Dynamic visualization of thrombopoiesis within bone marrow. Science, 317, 1767–1770.
- Jurk, K. & Kehrel, B.E. (2005) Platelets: physiology and biochemistry. Seminars in Thrombosis and Hemostasis, 31, 381–392.
- Kaluzhny, Y. & Ravid, K. (2004) Role of apoptotic processes in platelet biogenesis. Acta Haematologica, 111, 67–77.
- Kaluzhny, Y., Yu, G., Sun, S., Toselli, P.A., Nieswandt, B., Jackson, C.W. & Ravid, K. (2002) BclxL overexpression in megakaryocytes leads to impaired platelet fragmentation. Blood, 100, 1670–1678.
- Kaminska, J., Klimczak-Jajor, E., Skierski, J. & Bany-Laszewicz, U. (2008) Effects of inhibitor of Src kinases, SU6656, on differentiation of megakaryocytic progenitors and activity of alpha1,6-fucosyltransferase. Acta Biochimica Polonica, 55, 499–506.
- Kaufman, R.M., Airo, R., Pollack, S. & Crosby, W.H. (1965) Circulating megakaryocytes and platelet release in the lung. Blood, 26, 720–731.
- Kaushansky, K. (2006) Lineage-specific hematopoietic growth factors. New England Journal of Medicine, 354, 2034–2045.
- Kosaki, G. (2008) Platelet production by megakaryocytes: protoplatelet theory justifies cytoplasmic fragmentation model. International Journal of Hematology, 88, 255–267.
- Koudstaal, S., Jansen Of Lorkeers, S.J., Gaetani, R., Gho, J.M., van Slochteren, F.J., Sluijter, J.P., Doevendans, P.A., Ellison, G.M. & Chamuleau, S.A. (2013) Concise review: heart regeneration and the role of cardiac stem cells. Stem Cells Transl Med, 2, 434–443.
- Lambert, M.P., Sullivan, S.K., Fuentes, R., French, D.L. & Poncz, M. (2013) Challenges and promises for the development of donor-independent platelet transfusions. Blood, 121, 3319–3324.
- Lannutti, B.J. & Drachman, J.G. (2004) Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of hematopoietic cell lines and primary megakaryocytic progenitors. Blood, 103, 3736–3743.
- Lannutti, B.J., Blake, N., Gandhi, M.J., Reems, J.A. & Drachman, J.G. (2005) Induction of polyploidization in leukemic cell lines and primary bone marrow by Src kinase inhibitor SU6656. Blood, 105, 3875–3878.
- Larson, M.K. & Watson, S.P. (2006) Regulation of proplatelet formation and platelet release by integrin alpha IIb beta3. Blood, 108, 1509–1514.
- Lasky, L.C. & Sullenbarger, B. (2011) Manipulation of oxygenation and flow-induced shear stress can increase the in vitro yield of platelets from cord blood. Tissue Eng Part C Methods, 17, 1081–1088.
- Lerga, A., Crespo, P., Berciano, M., Delgado, M.D., Canelles, M., Cales, C., Richard, C., Ceballos, E., Gutierrez, P., Ajenjo, N., Gutkind, S. & Leon, J. (1999) Regulation of c-Myc and Max in megakaryocytic and monocytic-macrophagic differentiation of K562 cells induced by protein kinase C modifiers: c-Myc is down-regulated but does not inhibit differentiation. Cell Growth and Differentiation, 10, 639–654.
- Lim, W.F., Inoue-Yokoo, T., Tan, K.S., Lai, M.I. & Sugiyama, D. (2013) Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells. Stem Cell Res Ther, 4, 71.
- de Lima, M., McNiece, I., Robinson, S.N., Munsell, M., Eapen, M., Horowitz, M., Alousi, A., Saliba, R., McMannis, J.D., Kaur, I., Kebriaei, P., Parmar, S., Popat, U., Hosing, C., Champlin, R., Bollard, C., Molldrem, J.J., Jones, R.B., Nieto, Y., Andersson, B.S., Shah, N., Oran, B., Cooper, L.J., Worth, L., Qazilbash, M.H., Korbling, M., Rondon, G., Ciurea, S., Bosque, D., Maewal, I., Simmons, P.J. & Shpall, E.J. (2012) Cord-blood engraftment with ex vivo mesenchymal-cell coculture. New England Journal of Medicine, 367, 2305–2315.
- Lu, S.J., Li, F., Yin, H., Feng, Q., Kimbrel, E.A., Hahm, E., Thon, J.N., Wang, W., Italiano, J.E., Cho, J. & Lanza, R. (2011) Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice. Cell Research, 21, 530–545.
- Malara, A., Gruppi, C., Rebuzzini, P., Visai, L., Perotti, C., Moratti, R., Balduini, C., Tira, M.E. & Balduini, A. (2011) Megakaryocyte-matrix interaction within bone marrow: new roles for fibronectin and factor XIII-A. Blood, 117, 2476–2483.
- Matsubara, Y., Murata, M. & Ikeda, Y. (2012) Culture of megakaryocytes and platelets from subcutaneous adipose tissue and a preadipocyte cell line. Methods in Molecular Biology, 788, 249–258.
- Matsunaga, T., Tanaka, I., Kobune, M., Kawano, Y., Tanaka, M., Kuribayashi, K., Iyama, S., Sato, T., Sato, Y., Takimoto, R., Takayama, T., Kato, J., Ninomiya, T., Hamada, H. & Niitsu, Y. (2006) Ex vivo large-scale generation of human platelets from cord blood CD34+ cells. Stem Cells, 24, 2877–2887.
- Mattia, G., Vulcano, F., Milazzo, L., Barca, A., Macioce, G., Giampaolo, A. & Hassan, H.J. (2002) Different ploidy levels of megakaryocytes generated from peripheral or cord blood CD34+ cells are correlated with different levels of platelet release. Blood, 99, 888–897.
- Metcalf, D., Carpinelli, M.R., Hyland, C., Mifsud, S., Dirago, L., Nicola, N.A., Hilton, D.J. & Alexander, W.S. (2005) Anomalous megakaryocytopoiesis in mice with mutations in the c-Myb gene. Blood, 105, 3480–3487.
- Nakagawa, Y., Nakamura, S., Nakajima, M., Endo, H., Dohda, T., Takayama, N., Nakauchi, H., Arai, F., Fukuda, T. & Eto, K. (2013) Two differential flows in a bioreactor promoted platelet generation from human pluripotent stem cell-derived megakaryocytes. Experimental Hematology, 41, 742–748.
- Nishikii, H., Eto, K., Tamura, N., Hattori, K., Heissig, B., Kanaji, T., Sawaguchi, A., Goto, S., Ware, J. & Nakauchi, H. (2008) Metalloproteinase regulation improves in vitro generation of efficacious platelets from mouse embryonic stem cells. Journal of Experimental Medicine, 205, 1917–1927.
- Normand, G. & King, R.W. (2010) Understanding cytokinesis failure. Advances in Experimental Medicine and Biology, 676, 27–55.
- Ono, Y., Wang, Y., Suzuki, H., Okamoto, S., Ikeda, Y., Murata, M., Poncz, M. & Matsubara, Y. (2012) Induction of functional platelets from mouse and human fibroblasts by p45NF-E2/Maf. Blood, 120, 3812–3821.
- van den Oudenrijn, S., von dem Borne, A.E. & de Haas, M. (2000) Differences in megakaryocyte expansion potential between CD34(+) stem cells derived from cord blood, peripheral blood, and bone marrow from adults and children. Experimental Hematology, 28, 1054–1061.
- Pallotta, I., Lovett, M., Rice, W., Kaplan, D.L. & Balduini, A. (2009) Bone marrow osteoblastic niche: a new model to study physiological regulation of megakaryopoiesis. PLoS ONE, 4, e8359.
- Pallotta, I., Lovett, M., Kaplan, D.L. & Balduini, A. (2011) Three-dimensional system for the in vitro study of megakaryocytes and functional platelet production using silk-based vascular tubes. Tissue Eng Part C Methods, 17, 1223–1232.
- Patel, S.R., Hartwig, J.H. & Italiano, J.E. Jr (2005) The biogenesis of platelets from megakaryocyte proplatelets. Journal of Clinical Investigation, 115, 3348–3354.
- Perera, J.R., Jaiswal, P.K., Khan, W.S. & Adesida, A. (2012) Embryonic versus mesenchymal stem cells in cartilage repair. J Stem Cells, 7, 105–111.
- Piekny, A., Werner, M. & Glotzer, M. (2005) Cytokinesis: welcome to the Rho zone. Trends in Cell Biology, 15, 651–658.
- Pineault, N., Robert, A., Cortin, V. & Boyer, L. (2013) Ex vivo differentiation of cord blood stem cells into megakaryocytes and platelets. Methods in Molecular Biology, 946, 205–224.
- Poirault-Chassac, S., Nguyen, K.A., Pietrzyk, A., Casari, C., Veyradier, A., Denis, C.V. & Baruch, D. (2013) Terminal platelet production is regulated by von Willebrand factor. PLoS ONE, 8, e63810.
- Radley, J.M. & Scurfield, G. (1980) The mechanism of platelet release. Blood, 56, 996–999.
- Raslova, H., Kauffmann, A., Sekkai, D., Ripoche, H., Larbret, F., Robert, T., Le Roux, D.T., Kroemer, G., Debili, N., Dessen, P., Lazar, V. & Vainchenker, W. (2007) Interrelation between polyploidization and megakaryocyte differentiation: a gene profiling approach. Blood, 109, 3225–3234.
- Ravid, K., Lu, J., Zimmet, J.M. & Jones, M.R. (2002) Roads to polyploidy: the megakaryocyte example. Journal of Cellular Physiology, 190, 7–20.
- Rebulla, P. (2005) A mini-review on platelet refractoriness. Haematologica, 90, 247–253.
- Reems, J.A., Pineault, N. & Sun, S. (2010) In vitro megakaryocyte production and platelet biogenesis: state of the art. Transfusion Medicine Reviews, 24, 33–43.
- Rondina, M.T., Weyrich, A.S. & Zimmerman, G.A. (2013) Platelets as cellular effectors of inflammation in vascular diseases. Circulation Research, 112, 1506–1519.
- Schwertz, H., Koster, S., Kahr, W.H., Michetti, N., Kraemer, B.F., Weitz, D.A., Blaylock, R.C., Kraiss, L.W., Greinacher, A., Zimmerman, G.A. & Weyrich, A.S. (2010) Anucleate platelets generate progeny. Blood, 115, 3801–3809.
- Shin, J.W., Swift, J., Spinler, K.R. & Discher, D.E. (2011) Myosin-II inhibition and soft 2D matrix maximize multinucleation and cellular projections typical of platelet-producing megakaryocytes. Proceedings of the National Academy of Sciences of the United States of America, 108, 11458–11463.
- Shivdasani, R.A. (1996) The role of transcription factor NF-E2 in megakaryocyte maturation and platelet production. Stem Cells, 14, 112–115.
- Slichter, S.J., Bolgiano, D., Jones, M.K., Christoffel, T., Corson, J., Rose, L., Foley, J., Popovsky, M., Baril, L.L., Corda, T., Dincecco, D.M. & Snyder, E.L. (2006) Viability and function of 8-day-stored apheresis platelets. Transfusion, 46, 1763–1769.
- Sola-Visner, M.C., Christensen, R.D., Hutson, A.D. & Rimsza, L.M. (2007) Megakaryocyte size and concentration in the bone marrow of thrombocytopenic and nonthrombocytopenic neonates. Pediatric Research, 61, 479–484.
- Stachura, D.L., Chou, S.T. & Weiss, M.J. (2006) Early block to erythromegakaryocytic development conferred by loss of transcription factor GATA-1. Blood, 107, 87–97.
- Starck, J., Cohet, N., Gonnet, C., Sarrazin, S., Doubeikovskaia, Z., Doubeikovski, A., Verger, A., Duterque-Coquillaud, M. & Morle, F. (2003) Functional cross-antagonism between transcription factors FLI-1 and EKLF. Molecular and Cellular Biology, 23, 1390–1402.
- Stasi, R. (2012) How to approach thrombocytopenia. Hematology Am Soc Hematol Educ Program, 2012, 191–197.
- Straight, A.F. & Field, C.M. (2000) Microtubules, membranes and cytokinesis. Current Biology, 10, R760–R770.
- Sullenbarger, B., Bahng, J.H., Gruner, R., Kotov, N. & Lasky, L.C. (2009) Prolonged continuous in vitro human platelet production using three-dimensional scaffolds. Experimental Hematology, 37, 101–110.
- Sullivan, M.T., Cotten, R., Read, E.J. & Wallace, E.L. (2007) Blood collection and transfusion in the United States in 2001. Transfusion, 47, 385–394.
- Suzuki, N., Yamazaki, S., Yamaguchi, T., Okabe, M., Masaki, H., Takaki, S., Otsu, M. & Nakauchi, H. (2013) Generation of engraftable hematopoietic stem cells from induced pluripotent stem cells by way of teratoma formation. Molecular Therapy, 21, 1424–1431.
- Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K. & Yamanaka, S. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.
- Takayama, N. & Eto, K. (2012) Pluripotent stem cells reveal the developmental biology of human megakaryocytes and provide a source of platelets for clinical application. Cellular and Molecular Life Sciences, 69, 3419–3428.
- Takayama, N., Nishikii, H., Usui, J., Tsukui, H., Sawaguchi, A., Hiroyama, T., Eto, K. & Nakauchi, H. (2008) Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors. Blood, 111, 5298–5306.
- Takayama, N., Nishimura, S., Nakamura, S., Shimizu, T., Ohnishi, R., Endo, H., Yamaguchi, T., Otsu, M., Nishimura, K., Nakanishi, M., Sawaguchi, A., Nagai, R., Takahashi, K., Yamanaka, S., Nakauchi, H. & Eto, K. (2010a) Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells. Journal of Experimental Medicine, 207, 2817–2830.
- Takayama, M., Fujita, R., Suzuki, M., Okuyama, R., Aiba, S., Motohashi, H. & Yamamoto, M. (2010b) Genetic analysis of hierarchical regulation for Gata1 and NF-E2 p45 gene expression in megakaryopoiesis. Molecular and Cellular Biology, 30, 2668–2680.
- Thompson, A., Zhang, Y., Kamen, D., Jackson, C.W., Cardiff, R.D. & Ravid, K. (1996) Deregulated expression of c-myc in megakaryocytes of transgenic mice increases megakaryopoiesis and decreases polyploidization. Journal of Biological Chemistry, 271, 22976–22982.
- Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S. & Jones, J.M. (1998) Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.
- Tijssen, M.R. & Ghevaert, C. (2013) Transcription factors in late megakaryopoiesis and related platelet disorders. Jornal of Thrombosis and Haemostasis, 11, 593–604.
- Trowbridge, E.A., Martin, J.F., Slater, D.N., Kishk, Y.T., Warren, C.W., Harley, P.J. & Woodcock, B. (1984) The origin of platelet count and volume. Clinical Physics and Physiological Measurement, 5, 145–170.
- Tung, S.S., Parmar, S., Robinson, S.N., De Lima, M. & Shpall, E.J. (2010) Ex vivo expansion of umbilical cord blood for transplantation. Best Pract Res Clin Haematol, 23, 245–257.
- Ungerer, M., Peluso, M., Gillitzer, A., Massberg, S., Heinzmann, U., Schulz, C., Munch, G. & Gawaz, M. (2004) Generation of functional culture-derived platelets from CD34+ progenitor cells to study transgenes in the platelet environment. Circulation Research, 95, e36–e44.
- Wang, Y., Chou, B.K., Dowey, S., He, C., Gerecht, S. & Cheng, L. (2013) Scalable expansion of human induced pluripotent stem cells in the defined xeno-free E8 medium under adherent and suspension culture conditions. Stem Cell Res, 11, 1103–1116.
- Weiss, M.J., Keller, G. & Orkin, S.H. (1994) Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells. Genes and Development, 8, 1184–1197.
- Wendling, F. (1999) Thrombopoietin: its role from early hematopoiesis to platelet production. Haematologica, 84, 158–166.
- Whitaker, B.I. & Hinkins, S. (2011) The 2011 National Blood Collection and Utilization Survey Report. The United States Department of Health and Human Services, Washington, DC, USA.
- White, M.J. & Kile, B.T. (2010) Apoptotic processes in megakaryocytes and platelets. Seminars in Hematology, 47, 227–234.
- White, M.J., Schoenwaelder, S.M., Josefsson, E.C., Jarman, K.E., Henley, K.J., James, C., Debrincat, M.A., Jackson, S.P., Huang, D.C. & Kile, B.T. (2012) Caspase-9 mediates the apoptotic death of megakaryocytes and platelets, but is dispensable for their generation and function. Blood, 119, 4283–4290.
- Williamson, L.M. & Devine, D.V. (2013) Challenges in the management of the blood supply. Lancet, 381, 1866–1875.
- Xi, J., Zhu, H., Liu, D., Nan, X., Zheng, W., Liu, K., Shi, W., Chen, L., Lv, Y., Yan, F., Li, Y., Xie, X., Wang, Y., Yue, W., Xu, X., Wei, X., Zhu, J., Huang, X. & Pei, X. (2013) Infusion of megakaryocytic progenitor products generated from cord blood hematopoietic stem/progenitor cells: results of the phase 1 study. PLoS ONE, 8, e54941.
- Ye, L., Muench, M.O., Fusaki, N., Beyer, A.I., Wang, J., Qi, Z., Yu, J. & Kan, Y.W. (2013) Blood cell-derived induced pluripotent stem cells free of reprogramming factors generated by Sendai viral vectors. Stem Cells Transl Med, 2, 558–566.
- Zucker-Franklin, D. & Philipp, C.S. (2000) Platelet production in the pulmonary capillary bed: new ultrastructural evidence for an old concept. American Journal of Pathology, 157, 69–74.
Citing Literature
