Functional comparison of induced pluripotent stem cell- and blood-derived GPIIbIIIa deficient platelets.
oleh: Mathias Orban, Alexander Goedel, Jessica Haas, Kirstin Sandrock-Lang, Florian Gärtner, Christian Billy Jung, Barbara Zieger, Elvira Parrotta, Karin Kurnik, Daniel Sinnecker, Gerhard Wanner, Karl-Ludwig Laugwitz, Steffen Massberg, Alessandra Moretti
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2015-01-01 |
Deskripsi
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.