This year marks the tenth anniversary of the generation of induced pluripotent stem cells (iPSCs) by transcription factor-mediated somatic cell reprogramming. Takahashi and Yamanaka portray the path towards this ground-breaking discovery and discuss how, since then, research has focused on understanding the mechanisms underlying iPSC generation and on translating such advances to the clinic.

A decade of transcription factor-mediated reprogramming to pluripotency

The ability to generate induced pluripotent stem cells (iPSCs) from patients, and an increasingly refined capacity to differentiate these iPSCs into disease-relevant cell types, promises a new paradigm in drug development - one that positions human disease pathophysiology at the core of preclinical drug discovery. Disease models derived from iPSCs that manifest cellular disease phenotypes have been established for several monogenic diseases, but iPSCs can likewise be used for phenotype-based drug screens in complex diseases for which the underlying genetic mechanism is unknown. Here, we highlight recent advances as well as limitations in the use of iPSC technology for modelling a 'disease in a dish' and for testing compounds against human disease phenotypes in vitro. We discuss how iPSCs are being exploited to illuminate disease pathophysiology, identify novel drug targets and enhance the probability of clinical success of new drugs.

Induced pluripotent stem cells — opportunities for disease modelling and drug discovery

http://basicmed.med.ncku.edu.tw/public/project/1392-1396958609-1.pdf

Generation of Rejuvenated Antigen-Specific T Cells by Reprogramming to Pluripotency and Redifferentiation

Regenerative medicine offers the hope that cells for disease research and therapy might be created from readily available sources. To fulfil this promise, the cells available need to be converted into the desired cell types. We review two main approaches to accomplishing this goal: in vitro directed differentiation, which is used to push pluripotent stem cells, including embryonic stem cells or induced pluripotent stem cells, through steps similar to those that occur during embryonic development; and reprogramming (also known as transdifferentiation), in which a differentiated cell is converted directly into the cell of interest without proceeding through a pluripotent intermediate. We analyse the status of progress made using these strategies and highlight challenges that must be overcome to achieve the goal of cell-replacement therapy.

Turning straw into gold: directing cell fate for regenerative medicine

PROBLEM TO BE SOLVED: To provide an induced pluripotent stem cell prepared by reprograming a somatic cell without using an ovum, an embryo, a germ cell or an embryonic stem (ES) cell, a manufacturing method thereof, and use thereof.SOLUTION: An induced pluripotent stem cell is provided that is (1) derived from a cell other than germ cells and embryoblast, (2)produced without using an embryo, germ cell or embryonic stem (ES) cell, and (3) expresses endogenous Oct3/4 and Nanog. Factors, as nuclear reprogramming factors, are provided including gene products of three types of genes for respective gene products of Oct family genes, Klf family genes and Myc family genes, and a gene product of Sox family genes, and also, instead of a gene product of Myc family genes, a cytokine.

Yoko Umemura

Papers

Development of defective and persistent Sendai virus vector: a unique gene delivery/expression system ideal for cell reprogramming.