Induced Pluripotent Stem Cell-Derived Megakaryocytes and Platelets for Disease Modeling and Future Clinical Applications

Arterioscler Thromb Vasc Biol. 2017 Nov;37(11):2007-2013. doi: 10.1161/ATVBAHA.117.309197. Epub 2017 Oct 5.

Abstract

Platelets, derived from megakaryocytes, are anucleate cytoplasmic discs that circulate in the blood stream and play major roles in hemostasis, inflammation, and vascular biology. Platelet transfusions are used in a variety of medical settings to prevent life-threatening thrombocytopenia because of cancer therapy, other causes of acquired or inherited thrombocytopenia, and trauma. Currently, platelets used for transfusion purposes are donor derived. However, there is a drive to generate nondonor sources of platelets to help supplement donor-derived platelets. Efforts have been made by many laboratories to generate in vitro platelets and optimize their production and quality. In vitro-derived platelets have the potential to be a safer, more uniform product, and genetic manipulation could allow for better treatment of patients who become refractory to donor-derived units. This review focuses on potential clinical applications of in vitro-derived megakaryocytes and platelets, current methods to generate and expand megakaryocytes from pluripotent stem cell sources, and the use of these cells for disease modeling.

Keywords: blood platelets; hematopoiesis; humans; induced pluripotent stem cells; megakaryocytes.

Publication types

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

MeSH terms

  • Blood Platelets / metabolism
  • Blood Platelets / physiology*
  • Cell Line
  • Gene Expression Regulation, Developmental
  • Genetic Predisposition to Disease
  • Hematologic Diseases / blood
  • Hematologic Diseases / genetics
  • Hematologic Diseases / therapy
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / physiology*
  • Induced Pluripotent Stem Cells / transplantation
  • Megakaryocytes / metabolism
  • Megakaryocytes / physiology*
  • Megakaryocytes / transplantation
  • Phenotype
  • Platelet Transfusion
  • Thrombopoiesis*