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dc.contributor.authorGuan, Xin
dc.contributor.authorQin, Meng
dc.contributor.authorZhang, Yu
dc.contributor.authorWang, Yanan
dc.contributor.authorShen, Bin
dc.contributor.authorRen, Zhihua
dc.contributor.authorDing, Xinxin
dc.contributor.authorDai, Wei
dc.contributor.authorJiang, Yongping
dc.creator
dc.date.accessioned2017-05-25T14:18:52Z
dc.date.available2017-05-25T14:18:52Z
dc.date.issued2016
dc.identifier.citationGuan, X., Quin, M., Zhang, Y., Wang, Y., Shen, B., Ren, Z. . . . Jiang, Y. (2016). Safety and efficacy of megakaryocytes induced from hematopoietic stem cells in murine and nonhuman primate models. Stem Cells Translational Medicine, 6(3), 897-909. doi:10.5966/sctm.2016-0224en_US
dc.identifier.issn2157-6564
dc.identifier.urihttp://hdl.handle.net/1951/69245
dc.description.abstractBecause of a lack of platelet supply and a U.S. Food and Drug Administration-approved platelet growth factor, megakaryocytes have emerged as an effective substitute for alleviating thrombocytopenia. Here, we report the development of an efficient two-stage culture system that is free of stroma, animal components, and genetic manipulations for the production of functional megakaryocytes from hematopoietic stem cells. Safety and functional studies were performed in murine and nonhuman primate models. One human cryopreserved cord blood CD34+ cell could be induced ex vivo to produce up to 1.0 x 104 megakaryocytes that included CD41a+ and CD42b+ cells at 82.4% + 6.1% and 73.3% + 8.5% (mean + SD), respectively, yielding approximately 650-fold higher cell numbers than reported previously. Induced human megakaryocytic cells were capable of engrafting and producing functional platelets in the murine xenotransplantation model. In the nonhuman primate model, transplantation of primate megakaryocytic progenitors increased platelet count nadir and enhanced hemostatic function with no adverse effects. In addition, primate platelets were released in vivo as early as 3 hours after transplantation with autologous or allogeneic mature megakaryocytes and lasted for more than 48 hours. These results strongly suggest that large-scale induction of functional megakaryocytic cells is applicable for treating thrombocytopenic blood diseases in the clinic.en_US
dc.description.sponsorshipBiopharmaceutical R&D Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, People’s Republic of China Biopharmagen Corporation, Suzhou, People’s Republic of China Department of Laboratory Diagnosis, Suzhou Municipal Hospital Affiliated Nanjing Medical University, Suzhou, People’s Republic of China College of Nanoscale Science, SUNY Polytechnic Institute, Albany, New York, USA Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, New York, USAen_US
dc.language.isoenen_US
dc.publisherStem Cells Translational Medicineen_US
dc.subjectnonhuman primatesen_US
dc.subjecttransplantationen_US
dc.subjectexpansion and differentiationen_US
dc.subjecthematopoietic stem cellsen_US
dc.subjectmegakaryocytesen_US
dc.subjectthrombocytopeniaen_US
dc.subjectplateletsen_US
dc.subjectcord blooden_US
dc.titleSafety and efficacy of megakaryocytes induced from hematopoietic stem cells in murine and nonhuman primate modelsen_US
dc.title.alternativeStem Cells Translational Medicineen_US
dc.typeArticleen_US


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