TY - JOUR
T1 - Functional comparison of induced pluripotent stem cell-and blood-derived gpiibiiia deficient platelets
AU - Orban, Mathias
AU - Goedel, Alexander
AU - Haas, Jessica
AU - Sandrock-Lang, Kirstin
AU - Gärtner, Florian
AU - Jung, Christian Billy
AU - Zieger, Barbara
AU - Parrotta, Elvira
AU - Kurnik, Karin
AU - Sinnecker, Daniel
AU - Wanner, Gerhard
AU - Laugwitz, Karl Ludwig
AU - Massberg, Steffen
AU - Moretti, Alessandra
N1 - Publisher Copyright:
© 2015 Orban et al.
PY - 2015/1/21
Y1 - 2015/1/21
N2 - 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-hiPSCderived platelets recapitulate molecular and functional aspects of the disease and show comparable behavior to their native counterparts encouraging the further use of hiPSCbased disease models as well as the transition towards a clinical application.
AB - 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-hiPSCderived platelets recapitulate molecular and functional aspects of the disease and show comparable behavior to their native counterparts encouraging the further use of hiPSCbased disease models as well as the transition towards a clinical application.
UR - http://www.scopus.com/inward/record.url?scp=84956587222&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0115978
DO - 10.1371/journal.pone.0115978
M3 - Article
C2 - 25607928
AN - SCOPUS:84956587222
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - 0115978
ER -
