利用患者特异性诱导多能干细胞建立血小板无力症模型并通过CD41过表达恢复血小板聚集功能。
Modeling Glanzmann thrombasthenia using patient specific iPSCs and restoring platelet aggregation function by CD41 overexpression.
作者信息
Hu Liang, Du Lili, Zhao Yan, Li Wen, Ouyang Qi, Zhou Di, Lu Guangxiu, Lin Ge
机构信息
Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; National Engineering and Research Center of Human Stem Cells, Changsha 410013, China; Key Laboratory of Stem Cell and Reproductive Engineering, Ministry of Health, Changsha 410078, China.
Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou 510150, China.
出版信息
Stem Cell Res. 2017 Apr;20:14-20. doi: 10.1016/j.scr.2017.02.003. Epub 2017 Feb 11.
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.
Glanzmann血小板无力症（GT）是一种罕见的单基因出血性疾病，涉及无核血小板的聚集缺陷。在本研究中，我们从一名患有ITGA2B基因复杂异质突变的GT患者的皮肤成纤维细胞中生成了诱导多能干细胞（iPSC）。GT-iPSC可以成功分化为血小板（GT-iPS-血小板）。GT-iPS-血小板为CD41-/CD42b+/CD61-，在二磷酸腺苷（ADP）激活后血小板活化标志物（PAC-1）呈阴性。此外，GT-iPS-血小板在体外血小板聚集试验中存在缺陷。此外，野生型ITGA2B基因在GT-iPS血小板中的外源表达恢复了CD41表达和正常血小板聚集。我们的研究表明，患者特异性iPSC可能是基于干细胞的血小板疾病基因治疗的潜在靶点。
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