Scalable generation of universal platelets from human induced pluripotent stem cells

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Blood Platelets / cytology*
  • Blood Platelets / metabolism
  • Blood Platelets / ultrastructure
  • Cell Culture Techniques / methods
  • Cell Differentiation*
  • Cell Proliferation
  • Cells, Cultured
  • Gene Knockout Techniques
  • HLA Antigens / genetics
  • HLA Antigens / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / ultrastructure
  • Leukosialin / metabolism
  • Male
  • Megakaryocytes / cytology*
  • Megakaryocytes / metabolism
  • Megakaryocytes / ultrastructure
  • Mice, Inbred NOD
  • Mice, SCID
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Platelet Transfusion / methods
  • Reproducibility of Results
  • Transplantation, Heterologous
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / metabolism


  • Antigens, CD34
  • HLA Antigens
  • Leukosialin
  • Platelet Endothelial Cell Adhesion Molecule-1
  • beta 2-Microglobulin