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Cell Stem Cell. 2014 Apr 3;14(4):535-48. doi: 10.1016/j.stem.2014.01.011. Epub 2014 Feb 13.

Expandable megakaryocyte cell lines enable clinically applicable generation of platelets from human induced pluripotent stem cells.

Author information

1
Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 606-8507, Japan.
2
Department of Reprogramming Science, CiRA, Kyoto University, 606-8507, Japan.
3
Department of Anatomy, Ultrastructural Cell Biology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
4
Laboratory of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
5
Department of Cardiovascular Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Department of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi 329-0498, Japan.
6
Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 606-8507, Japan; Laboratory of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Electronic address: kojieto@cira.kyoto-u.ac.jp.

Abstract

The donor-dependent supply of platelets is frequently insufficient to meet transfusion needs. To address this issue, we developed a clinically applicable strategy for the derivation of functional platelets from human pluripotent stem cells (PSCs). This approach involves the establishment of stable immortalized megakaryocyte progenitor cell lines (imMKCLs) from PSC-derived hematopoietic progenitors through the overexpression of BMI1 and BCL-XL to respectively suppress senescence and apoptosis and the constrained overexpression of c-MYC to promote proliferation. The resulting imMKCLs can be expanded in culture over extended periods (4-5 months), even after cryopreservation. Halting the overexpression of c-MYC, BMI1, and BCL-XL in growing imMKCLs led to the production of CD42b(+) platelets with functionality comparable to that of native platelets on the basis of a range of assays in vitro and in vivo. The combination of robust expansion capacity and efficient platelet production means that appropriately selected imMKCL clones represent a potentially inexhaustible source of hPSC-derived platelets for clinical application.

PMID:
24529595
DOI:
10.1016/j.stem.2014.01.011
[Indexed for MEDLINE]
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