title: Functional comparison of induced pluripotent stem cell- and blood-derived GPIIbIIIa deficient platelets.
abstract: Human induced pluripotent stem cells (hiPSCs) represent a versatile tool to model genetic diseases and are a potential source for cell transfusion therapies. However, it remains elusive to which extent patient-specific hiPSC-derived cells functionally resemble their native counterparts. Here, we generated a hiPSC model of the primary platelet disease Glanzmann thrombasthenia (GT), characterized by dysfunction of the integrin receptor GPIIbIIIa, and compared side-by-side healthy and diseased hiPSC-derived platelets with peripheral blood platelets. Both GT-hiPSC-derived platelets and their peripheral blood equivalents showed absence of membrane expression of GPIIbIIIa, a reduction of PAC-1 binding, surface spreading and adherence to fibrinogen. We demonstrated that GT-hiPSC-derived platelets recapitulate molecular and functional aspects of the disease and show comparable behavior to their native counterparts encouraging the further use of hiPSC-based disease models as well as the transition towards a clinical application.
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximillians-Universität, Munich, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Orban
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Goedel
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Haas
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Sandrock-Lang
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximillians-Universität, Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Gärtner
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Christian Billy
authors.initials: CB
authors.lastname: Jung
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zieger
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; Department of Experimental and Clinical Medicine, University of Magna Graecia, Medical School, Catanzaro, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Parrotta
authors.affiliation: Paediatric Haemophilia Centre, Dr. von Hauner Children's Hospital, Ludwig-Maximillians-Universität, Munich, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Kurnik
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinnecker
authors.affiliation: Ultrastructural Research, Department Biology I, Biozentrum, Ludwig-Maximillians-Universität, Planegg-Martinsried, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wanner
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research)-partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Laugwitz
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximillians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research)-partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research)-partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Moretti
mesh_terms: D000293:Adolescent; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D013915:Thrombasthenia / Q000235:genetics / Q000473:pathology*
chemical_list: C056564:ITGA2B protein, human; D039421:Integrin alpha2; D005340:Fibrinogen