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    Safety and efficacy of megakaryocytes induced from hematopoietic stem cells in murine and nonhuman primate models

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    Safety and Efficacy of Megakaryocytes Induced from_Final.pdf (4.029Mb)
    Date
    2016
    Author
    Guan, Xin
    Qin, Meng
    Zhang, Yu
    Wang, Yanan
    Shen, Bin
    Ren, Zhihua
    Ding, Xinxin
    Dai, Wei
    Jiang, Yongping
    Publisher
    Stem Cells Translational Medicine
    Metadata
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    Subject
    nonhuman primates
    transplantation
    expansion and differentiation
    hematopoietic stem cells
    megakaryocytes
    thrombocytopenia
    platelets
    cord blood
    Abstract
    Because 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.
    URI
    http://hdl.handle.net/1951/69245
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    • SUNY Polytechnic Institute Faculty and Staff Research, Publications, and Creative Works [63]

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