Functional comparison of induced pluripotent stem cell- and blood-derived GPIIbIIIa deficient platelets
Summary
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 | Orban M, Goedel A, Haas J, Sandrock-Lang K, Gärtner F, Jung CB, Zieger B, Parrotta E, Kurnik K, Sinnecker D, Wanner G, Laugwitz KL, Massberg S, Moretti A |
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| Journal | PloS one |
| Publication Date | 2015;10(1):e0115978 |
| PubMed | 25607928 |
| PubMed Central | PMC4301811 |
| DOI | 10.1371/journal.pone.0115978 |