Pen A E, Jensen U B
Department of Molecular Biology and Genetics, Aarhus University, Tjele, Denmark.
Department of Clinical Genetics, Aarhus University Hospital, Skejby, Denmark.
Acta Neurol Scand. 2017 Jan;135(1):57-72. doi: 10.1111/ane.12545. Epub 2016 Jan 8.
Degenerative diseases of the brain have proven challenging to treat, let alone cure. One of the treatment options is the use of stem cell therapy, which has been under investigation for several years. However, treatment with stem cells comes with a number of drawbacks, for instance the source of these cells. Currently, a number of options are tested to produce stem cells, although the main issues of quantity and ethics remain for most of them. Over recent years, the potential of induced pluripotent stem cells (iPSCs) has been widely investigated and these cells seem promising for production of numerous different tissues both in vitro and in vivo. One of the major advantages of iPSCs is that they can be made autologous and can provide a sufficient quantity of cells by culturing, making the use of other stem cell sources unnecessary. As the first descriptions of iPSC production with the transcription factors Sox2, Klf4, Oct4 and C-Myc, called the Yamanaka factors, a variety of methods has been developed to convert somatic cells from all germ layers to pluripotent stem cells. Improvement of these methods is necessary to increase the efficiency of reprogramming, the quality of pluripotency and the safety of these cells before use in human trials. This review focusses on the current accomplishments and remaining challenges in the production and use of iPSCs for treatment of neurodegenerative diseases of the brain such as Alzheimer's disease and Parkinson's disease.
事实证明,脑部退行性疾病难以治疗,更别说治愈了。治疗选择之一是使用干细胞疗法,该疗法已研究数年。然而,干细胞治疗存在诸多弊端,比如这些细胞的来源。目前,人们测试了多种生产干细胞的方法,不过其中大多数方法仍存在数量和伦理等主要问题。近年来,诱导多能干细胞(iPSC)的潜力得到了广泛研究,这些细胞在体外和体内生成多种不同组织方面似乎很有前景。iPSC的主要优势之一在于它们可以实现自体化,并且通过培养能够提供足够数量的细胞,从而无需使用其他干细胞来源。自从首次描述利用转录因子Sox2、Klf4、Oct4和C-Myc(即山中因子)生产iPSC以来,已经开发出了多种将所有胚层的体细胞转化为多能干细胞的方法。在将这些方法用于人体试验之前,有必要改进这些方法,以提高重编程效率、多能性质量以及这些细胞的安全性。这篇综述聚焦于当前在生产和使用iPSC治疗脑部神经退行性疾病(如阿尔茨海默病和帕金森病)方面取得的成果以及仍然存在的挑战。