Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo. PO Box 1112. Blindern. 0317 Oslo. Norway.
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven. CT. 06520. USA.
Curr Gene Ther. 2013 Apr;13(2):99-110. doi: 10.2174/1566523211313020004.
Recent progress in the field of cellular reprogramming has opened up the doors to a new era of disease modelling, as pluripotent stem cells representing a myriad of genetic diseases can now be produced from patient tissue. These cells can be expanded and differentiated to produce a potentially limitless supply of the affected cell type, which can then be used as a tool to improve understanding of disease mechanisms and test therapeutic interventions. This process requires high levels of scrutiny and validation at every stage, but international standards for the characterisation of pluripotent cells and their progeny have yet to be established. Here we discuss the current state of the art with regard to modelling diseases affecting the ectodermal, mesodermal and endodermal lineages, focussing on studies which have demonstrated a disease phenotype in the tissue of interest. We also discuss the utility of pluripotent cell technology for the modelling of cancer and infectious disease. Finally, we spell out the technical and scientific challenges which must be addressed if the field is to deliver on its potential and produce improved patient outcomes in the clinic.
细胞重编程领域的最新进展为疾病建模开辟了一个新时代，因为现在可以从患者组织中产生代表多种遗传疾病的多能干细胞。这些细胞可以扩增和分化，以产生大量受影响的细胞类型，然后可以用作工具来改善对疾病机制的理解和测试治疗干预措施。该过程在每个阶段都需要高度的审查和验证，但尚未为多能细胞及其后代的特征制定国际标准。在这里，我们讨论了与影响外胚层、中胚层和内胚层谱系的疾病建模相关的最新技术，重点讨论了在感兴趣的组织中表现出疾病表型的研究。我们还讨论了多能细胞技术在癌症和传染病建模中的应用。最后，如果该领域要发挥其潜力并在临床上为患者带来更好的结果，我们阐明了必须解决的技术和科学挑战。
