title: Comparative analysis of human ex vivo-generated platelets vs megakaryocyte-generated platelets in mice: a cautionary tale.
abstract: Thrombopoiesis is the process by which megakaryocytes release platelets that circulate as uniform small, disc-shaped anucleate cytoplasmic fragments with critical roles in hemostasis and related biology. The exact mechanism of thrombopoiesis and the maturation pathways of platelets released into the circulation remain incompletely understood. We showed that ex vivo-generated murine megakaryocytes infused into mice release platelets within the pulmonary vasculature. Here we now show that infused human megakaryocytes also release platelets within the lungs of recipient mice. In addition, we observed a population of platelet-like particles (PLPs) in the infusate, which include platelets released during ex vivo growth conditions. By comparing these 2 platelet populations to human donor platelets, we found marked differences: platelets derived from infused megakaryocytes closely resembled infused donor platelets in morphology, size, and function. On the other hand, the PLP was a mixture of nonplatelet cellular fragments and nonuniform-sized, preactivated platelets mostly lacking surface CD42b that were rapidly cleared by macrophages. These data raise a cautionary note for the clinical use of human platelets released under standard ex vivo conditions. In contrast, human platelets released by intrapulmonary-entrapped megakaryocytes appear more physiologic in nature and nearly comparable to donor platelets for clinical application.
authors: Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA;
authors: Yuhuan
authors: Y
authors: Wang
authors: Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA;
authors: Vincent
authors: V
authors: Hayes
authors: Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA; Department of Transplantation, Jagiellonian University, Medical College, Cracow, Poland;
authors: Danuta
authors: D
authors: Jarocha
authors: Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA; Departments of Pediatrics and Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;
authors: Xiuli
authors: X
authors: Sim
authors: Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA; and.
authors: Dawn C
authors: DC
authors: Harper
authors: Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA;
authors: Rudy
authors: R
authors: Fuentes
authors: Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA;
authors: Spencer K
authors: SK
authors: Sullivan
authors: Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA; Departments of Pediatrics and Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;
authors: Paul
authors: P
authors: Gadue
authors: Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA; Departments of Pediatrics and Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;
authors: Stella T
authors: ST
authors: Chou
authors: Fred Hutchinson Cancer Research Center, Seattle, WA.
authors: Beverly J
authors: BJ
authors: Torok-Storb
authors: Departments of Pediatrics and Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA; and.
authors: Michael S
authors: MS
authors: Marks
authors: Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA; Departments of Pediatrics and Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;
authors: Deborah L
authors: DL
authors: French
authors: Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA; Departments of Pediatrics and Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;
authors: Mortimer
authors: M
authors: Poncz
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D051379:Mice; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D034061:Thrombopoiesis
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex