Stem Cell Reports
Volume 3, Issue 5, 11 November 2014, Pages 817-831
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Article
Scalable Generation of Universal Platelets from Human Induced Pluripotent Stem Cells

https://doi.org/10.1016/j.stemcr.2014.09.010Get rights and content
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Highlights

  • Large-scale production of platelets from human iPSCs under defined conditions

  • iPSC platelets are functional both in vivo and in vitro

  • Knockout of β2-microglobulin gene in iPSCs generates universal platelets

Summary

Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid “surge” capacity when large numbers of platelets are needed. Ultrastructural/morphological analyses show no major differences between iPSC platelets and human blood platelets. iPSC platelets form aggregates, lamellipodia, and filopodia after activation and circulate in macrophage-depleted animals and incorporate into developing mouse thrombi in a manner identical to human platelets. By knocking out the β2-microglobulin gene, we have generated platelets that are negative for the major histocompatibility antigens. The scalable generation of HLA-ABC-negative platelets from a renewable cell source represents an important step toward generating universal platelets for transfusion as well as a potential strategy for the management of platelet refractoriness.

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).