诱导性多功能干细胞ips的研究进展与应用前景.docxVIP

诱导性多潜能干细胞的研究进展和应用前景学号:201111630姓名:李明君AbstractRecent reports demonstrate that mouse somaticcells can be directly reprogrammed into pluripotentembryonic stem (ES) cell-like cells byin vitro introduction of four transcription factors, Oct4, Sox2, c-Myc and Klf4. These cells aredesignated as induced pluripotent stem (iPS) cells. Similarly, the transfection with these fourtranscription factors or a cocktail of Oct4, Sox2, Nanog and LIN28 has been shown to be sufficientto reprogram human somatic cells to iPScells that are indistinguishable from human EScells. Since reactivation of the c-Myc transgenehas been reported to increase tumorigenicityin the chimeras and progeny mice, amodifiedprotocol with only three factors (Oct4, Sox2 andKlf4) has been recently used to make mouse andhuman iPS cells fromadultdermalfibroblasts. Differentiated somatic cells can be directly reprogrammed into induced pluripotent stem ( iPS) cells in vitro. Similarly to embryonic stem ( ES) cells,iPS cellshavepluripotency to differentiate into allcell types and capability toself-renew themselvesindefinitely. Without immune rejection and ethical issues,patient-specific iPS cells promise to be an ideal tool for regenerative medicine,drug screening,and toxicity testing.摘要研究证实采用体外导入Oct4、Sox2、c-Myc和Klf4等4个转录因子可将小鼠体细胞直接重构成为ES细胞样的多潜能细胞, 这类细胞被命名为诱导性多潜能干细胞(iPS细胞). 同样,转染上述因子或Oct4、Sox2、Nanog、LIN28等4个因子也能够使人类体细胞重构为iPS细胞, 后者与人类ES细胞的基本特征相似. 据报道, 由于转染基因c-Myc的重新激活可使嵌合体和子代小鼠的肿瘤发生增加, 故近期建立了一种仅使用3个因子(Oct4、Sox2和Klf4)的改良方案, 也可将成年小鼠和成人皮肤成纤维细胞诱导转化为iPS细胞. 近期文献资料表明, 人类iPS细胞系对于制备疾病的新模型和药物研究有帮助, 但其用于移植治疗的应用前景则需要进一步加以考证.分化成熟的体细胞可在体外被重编程为诱导性多潜能干细胞,后者具有与胚胎干细胞相似的自我更新能力和发育多潜能性,同时避免了免疫排斥和伦理问题。患者特异性的诱导性多潜能干细胞将成为再生医学、药物筛选毒理测试的理想工具。关键词: 基因转染; 体细胞重构; 干细胞; 转录因子0引言干细胞(stem cells)是人体及其各种组织细胞的初始来源, 其最显著的生物学特征是既有自我更新和不断增殖的能力, 又有多向分化的潜能.干细胞根据不同的来源分为成体干细胞(somaticstem cells)和胚胎干细胞(embryonic stem cells, ES细胞). 成体干细胞包括骨髓间充质干细胞、胰腺干细胞、神经干细胞等成体组织中存在的干细胞, 理论上在特定条件下可分化为特定的组织器官, 是修复和再生的基础. ES细胞是从着床前的早期胚胎(囊胚)内细胞团中分离得到的一种二倍体细胞, 理论上具有发育和分化成为机体内几乎所有组织细胞类型的