Enhanced generation of megakaryocytes from umbilical cord blood-derived CD34⁺ cells expanded in the presence of two nutraceuticals, docosahexanoic acid and arachidonic acid, as supplements to the cytokine-containing medium

References

• Kratz-Albers K, Scheding S, Mohle R, Buhring HJ, Baum CM, McKearn JP, . Effective ex vivo generation of megakaryocytic cells from mobilized peripheral blood CD34+ cells with stem cell factor and promegapoietin. Exp Hematol. 2000;28:335–46.
   PubMed Web of Science ®Google Scholar
• Lin S, Liu S, Sun X, Yang M. [Studies on ex vivo expansion of megakaryocytic progenitor and its application: review]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2006;14:835–9.
   Google Scholar
• Drayer AL, Smit Sibinga CT, Esselink MT, de Wolf JT, Vellenga E. In vitro megakaryocyte expansion in patients with delayed platelet engraftment after autologous stem cell transplantation. Ann Hematol. 2002;81:192–7.
   PubMedGoogle Scholar
• Laplante AF, Germain L, Auger FA, Moulin V. Mechanisms of wound reepithelialization: hints from a tissue-engineered reconstructed skin to long-standing questions. FASEB J. 2001;15:2377–89.
   PubMed Web of Science ®Google Scholar
• Matsunaga T, Tanaka I, Kobune M, Kawano Y, Tanaka M, Kuribayashi K, . Ex vivo large-scale generation of human platelets from cord blood CD34+ cells. Stem Cells. 2006;24:2877–87.
   PubMed Web of Science ®Google Scholar
• Patel SR, Hartwig JH, Italiano JE, Jr. The biogenesis of platelets from megakaryocyte proplatelets. J Clin Invest. 2005;115:3348–54.
   PubMed Web of Science ®Google Scholar
• Bertolini F, Battaglia M, Pedrazzoli P, Da Prada GA, Lanza A, Soligo D, . Megakaryocytic progenitors can be generated ex vivo and safely administered to autologous peripheral blood progenitor cell transplant recipients. Blood. 1997;89:2679–88.
   PubMed Web of Science ®Google Scholar
• Decaudin D, Vantelon JM, Bourhis JH, Farace F, Bonnet ML, Guillier M, . Ex vivo expansion of megakaryocyte precursor cells in autologous stem cell transplantation for relapsed malignant lymphoma. Bone Marrow Transplant. 2004;34:1089–93.
   PubMed Web of Science ®Google Scholar
• Scheding S, Bergmannn M, Rathke G, Vogel W, Brugger W, Kanz L. Additional transplantation of ex vivo generated megakaryocytic cells after high-dose chemotherapy. Haematologica. 2004;89:630–1.
   PubMed Web of Science ®Google Scholar
• Kanamaru S, Kawano Y, Watanabe T, . Low numbers of megakaryocyte progenitors in grafts of cord blood cells may result in delayed platelet recovery after cord blood cell transplant. Stem Cells. 2000;18:190–5.
   Google Scholar
• Chang Y, Bluteau D, Debili N, Vainchenker W. From hematopoietic stem cells to platelets. J Thromb Haemost. 2007;5(Suppl 1):318–27.
   PubMed Web of Science ®Google Scholar
• Gibbins J and Mahaut-Smith M. Platelets & Megakaryocytes Vol.1. Functional assay. Methods in Mol. Biol, 2004; Page nos. 29-46, 225-268, 293-308. Humana Press Inc, Totowa, New Jersy, USA.
   Google Scholar
• Pick M, Eldor A, Grisaru D, Zander AR, Shenhav M, Deutsch VR. Ex vivo expansion of megakaryocyte progenitors from cryopreserved umbilical cord blood. A potential source of megakaryocytes for transplantation. Exp Hematol. 2002;30:1079–87.
   PubMedGoogle Scholar
• Bruno S, Gunetti M, Gammaitoni L, Dane A, Cavalloni G, Sanavio F, . In vitro and in vivo megakaryocyte differentiation of fresh and ex-vivo expanded cord blood cells: rapid and transient megakaryocyte reconstitution. Haematologica. 2003;88:379–87.
   PubMed Web of Science ®Google Scholar
• Bruno S, Gunetti M, Gammaitoni L, Perissinotto E, Caione L, Sanavio F, . Fast but durable megakaryocyte repopulation and platelet production in NOD/SCID mice transplanted with ex-vivo expanded human cord blood CD34+ cells. Stem Cells. 2004;22:135–43.
   PubMed Web of Science ®Google Scholar
• Sun L, Tan P, Yap C, Hwang W, Koh LP, Lim CK, . In vitro biological characteristics of human cord blood-derived megakaryocytes. Ann Acad Med Singapore. 2004;33: 570–5.
   Google Scholar
• De Bruyn C, Delforge A, Martiat P, Bron D. Ex vivo expansion of megakaryocyte progenitor cells: cord blood versus mobilized peripheral blood. Stem Cells Dev. 2005;14: 415–24.
   PubMed Web of Science ®Google Scholar
• Ju XL, Shi Q, Huang ZW, Hou HS, Sun NZ, Zhao Y, . [In vitro expansion and function of cord blood megakaryocyte]. Zhonghua Er Ke Za Zhi 2007;45:64–8.
   Google Scholar
• Cortin V, Pineault N, Garnier A. Ex vivo megakaryocyte expansion and platelet production from human cord blood stem cells. Methods Mol Biol. 2009;482:109–26.
   PubMedGoogle Scholar
• Boyer L, Robert A, Proulx C, Pineault N. Increased production of megakaryocytes near purity from cord blood CD34+ cells using a short two-phase culture system. J Immunol Methods. 2008;332:82–91.
   PubMed Web of Science ®Google Scholar
• Van den Oudenrijn S, dem Borne AE, de Haas M. Differences in megakaryocyte expansion potential between CD34+ stem cells derived from cord blood, peripheral blood, and bone marrow from adults and children. Exp Hematol. 2000;28:1054–61.
   PubMed Web of Science ®Google Scholar
• Mattia G, Milazzo L, Vulcano F, Pascuccio M, Macioce G, Hassan HJ, . Long-term platelet production assessed in NOD/SCID mice injected with cord blood CD34+ cells, thrombopoietin-amplified in clinical grade serum-free culture. Exp Hematol. 2008;36:244–52.
   PubMedGoogle Scholar
• Chen TW, Yao CL, Chu IM, Chuang TL, Hsieh TB, Hwang SM. Large generation of megakaryocytes from serum-free expanded human CD34+ cells. Biochem Biophys Res Commun. 2009;378:112–17.
   PubMed Web of Science ®Google Scholar
• Chen TW, Yao CL, Chu IM, Chuang TL, Hsieh TB, Hwang SM. Characterization and transplantation of induced megakaryocytes from hematopoietic stem cells for rapid platelet recovery by a two-step serum-free procedure. Exp Hematol 2009;37:1330–9.
   PubMedGoogle Scholar
• Feng Y, Zhang L, Xiao ZJ, Li B, Liu B, Fan CG, . An effective and simple expansion system for megakaryocyte progenitor cells using a combination of heparin with thrombopoietin and interleukin-11. Exp Hematol. 2005;33:1537–43.
   PubMed Web of Science ®Google Scholar
• Kashiwakura I, Takahashi K, Monzen S, Nakamura T, Takagaki K. Ex vivo expansions of megakaryocytopoiesis from placental and umbilical cord blood CD34+ cells in serum-free culture supplemented with proteoglycans extracted from the nasal cartilage of salmon heads and the nasal septum cartilage of whale. Life Sci. 2008;82:1023–31.
   PubMedGoogle Scholar
• O'Brien JJ, Spinelli SL, Tober J, Blumberg N, Francis CW, Taubman MB, . 15-deoxy-delta12,14-PGJ2 enhances platelet production from megakaryocytes. Blood. 2008;112:4051–60.
   PubMed Web of Science ®Google Scholar
• Morris D. H. Flax - A Health and Nutrition Primer, Fourth Edition, 2007; 20-27. published by Flax Council of Canada, Winnipeg, MB R3B0T6, Canada.
   Google Scholar
• De Lorgeril M. Essential polyunsaturated fatty acids, inflammation, atherosclerosis and cardiovascular diseases. Subcell Biochem. 2007;42:283–97.
   PubMedGoogle Scholar
• Mori TA, Woodman RJ. The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans. Curr Opin Clin Nutr Metab Care. 2006;9:95–104.
   PubMed Web of Science ®Google Scholar
• Brand A, Schonfeld E, Isharel I, Yavin E. Docosahexaenoic acid-dependent iron accumulation in oligodendroglia cells protects from hydrogen peroxide-induced damage. J Neurochem. 2008;105:1325–35.
   PubMed Web of Science ®Google Scholar
• Krishnamurti C, Stewart MW, Cutting MA, Rothwell SW. Assessment of omega-fatty-acid-supplemented human platelets for potential improvement in long-term storage. Thromb Res. 2002;105:139–45.
   Google Scholar
• Eritsland J. Safety considerations of polyunsaturated fatty acids. Am J Clin Nutr. 2000;71:197S–201S.
   PubMed Web of Science ®Google Scholar
• Holub BJ. Clinical nutrition. 4. Omega-3 fatty acids in cardiovascular care. Canadian Medical Association Journal. 2002;166:608–15.
   PubMed Web of Science ®Google Scholar
• Rizzo MT. The role of arachidonic acid in normal and malignant hematopoiesis. Prostaglandins Leukot Essent Fatty Acids. 2002;66:57–69.
   Google Scholar
• Nelson GJ, Schmidt PS, Bartolini GL, Kelley DS, Kyle D. The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids. 1997;32:1129–36.
   PubMed Web of Science ®Google Scholar
• Nelson GJ, Schmidt PC, Bartolini G, Kelley DS, Kyle D. The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids. 1997;32:421–5.
   Google Scholar
• Vericel E, Polette A, Bacot S, Calzada C, Lagarde M. Pro- and antioxidant activities of docosahexaenoic acid on human blood platelets. J Thromb Haemost. 2003;1:566–72.
   PubMed Web of Science ®Google Scholar
• Won JH, Cho SD, Park SK, Lee GT, Baick SH, Suh WS, . Thrombopoietin is synergistic with other cytokines for expansion of cord blood progenitor cells. J Hematother Stem Cell Res. 2000;9:465–73.
   PubMedGoogle Scholar
• Xu Y, Kashiwakura I, Takahashi TA. High sensitivity of megakaryocytic progenitor cells contained in placental/umbilical cord blood to the stresses during cryopreservation. Bone Marrow Transplant. 2004;34:537–43.
   PubMedGoogle Scholar
• Miyazaki R, Ogata H, Iguchi T, Sogo S, Kushida T, Ito T, . Comparative analyses of megakaryocytes derived from cord blood and bone marrow. Br J Haematol. 2000;108:602–9.
   PubMed Web of Science ®Google Scholar
• Drayer AL, Sibinga CT, Blom NR, De Wolf JT, Vellenga E. The in vitro effects of cytokines on expansion and migration of megakaryocyte progenitors. Br J Haematol. 2000;109: 776–84.
   PubMed Web of Science ®Google Scholar
• Tijssen MR, van der Schoot CE, Voermans C, Zwaginga JJ. The (patho)physiology of megakaryocytopoiesis: from thrombopoietin in diagnostics and therapy to ex vivo generated cellular products. Vox Sang. 2004;87(Suppl 2): 52–5.
   Google Scholar
• Heemskerk JW, Vossen RC, Dam-Mieras MC. Polyunsaturated fatty acids and function of platelets and endothelial cells. Curr Opin Lipidol. 1996;7:24–29.
   Google Scholar
• Szalai G, LaRue AC, Watson DK. Molecular mechanisms of megakaryopoiesis. Cell Mol Life Sci. 2006;63:2460–76.
   PubMed Web of Science ®Google Scholar
• Hamada T, Mohle R, Hesselgesser J, Hoxie J, Nachman RL, Moore MA, . Transendothelial migration of megakaryocytes in response to stromal cell-derived factor 1 (SDF-1) enhances platelet formation. J Exp Med. 1998;188:539–48.
   PubMed Web of Science ®Google Scholar
• Riviere C, Subra F, Cohen-Solal K, Cordette-Lagarde V, Letestu R, Auclair C, . Phenotypic and functional evidence for the expression of CXCR4 receptor during megakaryocytopoiesis. Blood. 1999;93:1511–23.
   PubMed Web of Science ®Google Scholar
• Ryu KH, Chun S, Carbonierre S, Im SA, Kim HL, Shin MH, . Apoptosis and megakaryocytic differentiation during ex vivo expansion of human cord blood CD34+ cells using thrombopoietin. Br J Haematol. 2001;113:470–8.
   Google Scholar
• Kaushansky K. The enigmatic megakaryocyte gradually reveals its secrets. Bioessays. 1999;21:353–60.
   PubMed Web of Science ®Google Scholar
• Zeuner A, Signore M, Martinetti D, Bartucci M, Peschle C, De Maria R. Chemotherapy-induced thrombocytopenia derives from the selective death of megakaryocyte progenitors and can be rescued by stem cell factor. Cancer Res. 2007;67:4767–73.
   PubMed Web of Science ®Google Scholar
• Arita K, Kobuchi H, Utsumi T, Takehara Y, Akiyama J, Horton AA, . Mechanism of apoptosis in HL-60 cells induced by n-3 and n-6 polyunsaturated fatty acids. Biochem Pharmacol. 2001;62:821–8.
   PubMed Web of Science ®Google Scholar
• Cao Y, Pearman AT, Zimmerman GA, McIntyre TM, Prescott SM. Intracellular unesterified arachidonic acid signals apoptosis. Proc Natl Acad Sci USA. 2000;97: 11280–5.
   PubMed Web of Science ®Google Scholar
• Mu YM, Yanase T, Nishi Y, Tanaka A, Saito M, Jin CH, . Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells. Endocrinology. 2001;142: 3590–7.
   PubMed Web of Science ®Google Scholar
• Tang DG, Guan KL, Li L, Honn KV, Chen YQ, Rice RL, . Suppression of W256 carcinosarcoma cell apoptosis by arachidonic acid and other polyunsaturated fatty acids. Int J Cancer. 1997;72:1078–87.
   Google Scholar
• Florent S, Malaplate-Armand C, Youssef I, Kriem B, Koziel V, Escanye MC, . Docosahexaenoic acid prevents neuronal apoptosis induced by soluble amyloid-beta oligomers. J Neurochem. 2006;96:385–95.
   PubMed Web of Science ®Google Scholar
• Papadimitriou A, King AJ, Jones PM, Persaud SJ. Anti-apoptotic effects of arachidonic acid and prostaglandin E2 in pancreatic beta-cells. Cell Physiol Biochem. 2007;20:607–16.
   PubMedGoogle Scholar
• Ivanovic Z, Duchez P, Dazey B, Hermitte F, Lamrissi-Garcia I, Mazurier F, . A clinical-scale expansion of mobilized CD34+ hematopoietic stem and progenitor cells by use of a new serum-free medium. Transfusion. 2006;46:126–31.
   Google Scholar
• Guillot N, Debard C, Calzada C, Vidal H, Lagarde M, Vericel E. Effects of docosahexaenoic acid on some megakaryocytic cell gene expression of some enzymes controlling prostanoid synthesis. Biochem Biophys Res Commun. 2008;372:924–8.
   PubMedGoogle Scholar
• Richard D, Kefi K, Barbe U, Bausero P, Visioli F. Polyunsaturated fatty acids as antioxidants. Pharmacol Res. 2008;57:451–5.
   PubMed Web of Science ®Google Scholar
• Maziere C, Conte MA, Degonville J, Ali D, Maziere JC. Cellular enrichment with polyunsaturated fatty acids induces an oxidative stress and activates the transcription factors AP1 and NFkappaB. Biochem Biophys Res Commun. 1999;265: 116–22.
   PubMed Web of Science ®Google Scholar
• McCrann DJ, Eliades A, Makitalo M, Matsuno K, Ravid K. Differential expression of NADPH oxidases in megakaryocytes and their role in polyploidy. Blood. 2009;114:1243–9.
   PubMed Web of Science ®Google Scholar