title: Understanding platelet generation from megakaryocytes: implications for in vitro-derived platelets.
abstract: Platelets are anucleate cytoplasmic discs derived from megakaryocytes that circulate in the blood and have major roles in hemostasis, thrombosis, inflammation, and vascular biology. Platelet transfusions are required to prevent the potentially life-threatening complications of severe thrombocytopenia seen in a variety of medical settings including cancer therapy, trauma, and sepsis. Platelets used in the clinic are currently donor-derived which is associated with concerns over sufficient availability, quality, and complications due to immunologic and/or infectious issues. To overcome our dependence on donor-derived platelets for transfusion, efforts have been made to generate in vitro-based platelets. Work in this area has advanced our understanding of the complex processes that megakaryocytes must undergo to generate platelets both in vivo and in vitro. This knowledge has also defined the challenges that must be overcome to bring in vitro-based platelet manufacturing to a clinical reality. This review will focus on our understanding of committed megakaryocytes and platelet release in vivo and in vitro, and how this knowledge can guide the development of in vitro-derived platelets for clinical application.
authors.affiliation: Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Cell and Molecular Biology, University of Pennsylvania School of Medicine, Philadelphia, PA;
authors.forename: Xiuli
authors.initials: X
authors.lastname: Sim
authors.affiliation: Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA;
authors.forename: Mortimer
authors.initials: M
authors.lastname: Poncz
authors.affiliation: Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia PA; and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors.forename: Paul
authors.initials: P
authors.lastname: Gadue
authors.affiliation: Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia PA; and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: French
mesh_terms: D000818:Animals; D001782:Blood Donors; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D017713:Platelet Transfusion