Modeling Glanzmann thrombasthenia using patient specific iPSCs and restoring platelet aggregation function by CD41 overexpression

• DOI: 10.1016/j.scr.2017.02.003
• Publication Date: 2017-02-11T12:00:58Z
• Authors: Liang Hu; Lili Du; Yan Zhao; Wen Li; Qi Ouyang; Di Zhou; Guangxiu Lu; Ge Lin
• Keywords: Blood Platelets; Platelet Membrane Glycoprotein IIb; 0301 basic medicine; Platelet Aggregation; QH301-705.5; DNA Mutational Analysis; Induced Pluripotent Stem Cells; Karyotype; Integrin alpha2; Mice, Nude; Cell Line; Mice; 03 medical and health sciences; CD41; Animals; Humans; Biology (General); Medicine(all); Polymorphism, Genetic; Base Sequence; Glanzmann thrombasthenia; Platelet; Teratoma; Dual Specificity Phosphatase 2; Cell Differentiation; Cell Biology; Fibroblasts; Cellular Reprogramming; 3. Good health; Induced pluripotent stem cells; Developmental Biology; Thrombasthenia

Glanzmann thrombasthenia (GT) is a rare monogenic hemorrhagic disorder involving aggregation defect of non-nuclear platelets. In this study we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of a GT patient with complex heterogeneous mutations of ITGA2B gene. GT-iPSCs could be successfully differentiated into platelets (GT-iPS-platelets). GT-iPS-platelets were CD41-/CD42b+/CD61- and were platelet activation marker (PAC-1) negative after adenosine diphosphate (ADP) activation. Furthermore, GT-iPS-platelets were defective in platelet aggregation tests in vitro. Moreover, exogenous expression of the wild-type ITGA2B gene in GT-iPS platelets restored CD41 expression and normal platelet aggregation. Our study suggested that patient-specific iPSCs could be a potential target of stem cell based gene therapy for platelet diseases.