Journal
CELL STEM CELL
Volume 14, Issue 4, Pages 535-548Publisher
CELL PRESS
DOI: 10.1016/j.stem.2014.01.011
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Funding
- MEXT
- Project of Realization of Regenerative Medicine and Highway Program from MEXT/ JST
- A-STEP
- CREST from JST
- Ministry of Health Labor and Welfare
- JSPS
- Grants-in-Aid for Scientific Research [25860236] Funding Source: KAKEN
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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.
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