Safety and efficacy of megakaryocytes induced from hematopoietic stem cells in murine and nonhuman primate models
Loading...
Authors
Guan, Xin
Qin, Meng
Zhang, Yu
Wang, Yanan
Shen, Bin
Ren, Zhihua
Ding, Xinxin
Dai, Wei
Jiang, Yongping
Issue Date
2016
Type
Article
Language
en
Keywords
nonhuman primates , transplantation , expansion and differentiation , hematopoietic stem cells , megakaryocytes , thrombocytopenia , platelets , cord blood
Alternative Title
Stem Cells Translational Medicine
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.
Description
Citation
Guan, 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.2016-0224
Publisher
Stem Cells Translational Medicine
License
Journal
Volume
Issue
PubMed ID
DOI
ISSN
2157-6564