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Stem Cell Reports. 2014 Nov 11;3(5):817-31. doi: 10.1016/j.stemcr.2014.09.010. Epub 2014 Oct 16.

Scalable generation of universal platelets from human induced pluripotent stem cells.

Author information

1
Advanced Cell Technology, Marlborough, MA 01752, USA.
2
Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
3
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115.
4
Allele Biotechnology, San Diego, CA 92121, USA.
5
MacLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
6
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, MA 02115, USA.
7
Advanced Cell Technology, Marlborough, MA 01752, USA. Electronic address: rlanza@advancedcell.com.

Abstract

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.

PMID:
25418726
PMCID:
PMC4235139
DOI:
10.1016/j.stemcr.2014.09.010
[Indexed for MEDLINE]
Free PMC Article

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