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目的:利用诱导多能性干细胞(iPSC)技术建立原发性骨髓纤维化(PMF)诱导多能性干细胞系,为研究血液病的发生发展提供一个实验模型。方法:采用非基因整合型质粒重编程携带JAK2V617F突变的PMF患者骨髓来源的单个核细胞,诱导生成该患者特异的iPS细胞株。结果:采用此方法建立的iPS细胞株,在体外能够稳定传代,无外源性基因整合,多能性基因表达水平与人胚胎干细胞类似,在体内具有形成三胚层结构的能力。测序结果显示,所建立的患者的iPS细胞株携带不同负荷的JAK2V617F突变。结论:成功地建立非基因整合的PMF患者特异的iPS细胞株,这为研究PMF的发病机制、化疗药物筛选及实现精准化治疗提供了一个重要的疾病模型。
OBJECTIVE: To establish a model of pluripotent stem cell line induced by primary myelofibrosis (PMF) using induced pluripotent stem cells (iPSC) technique and to provide an experimental model for studying the occurrence and development of hematological diseases. METHODS: Bone marrow-derived mononuclear cells from PMF patients carrying the JAK2V617F mutation were reprogrammed using non-gene integrating plasmids to induce the generation of this patient-specific iPS cell line. Results: The iPS cell line established by this method can stably pass in vitro with no exogenous gene integration. The expression level of pluripotency gene is similar to that of human embryonic stem cells and has the ability of forming the three germ layers in vivo. Sequencing results showed that the iPS cell lines of the established patients carried different loads of the JAK2V617F mutation. Conclusion: The successful establishment of non-genetically-integrated PMF patient-specific iPS cell lines provides an important disease model for studying the pathogenesis of PMF, chemotherapeutic drug screening and precise treatment.