The constant visitation to the initial reprogramming strategy by many researchers worldwide has led to the understanding of the molecular bases and to the improvement of the cell reprogramming process, bringing iPSC closer to safe clinical applications. We also present the current and future applications and therapeutic strategies involving iPSC to improve health. Here, we introduce some of the challenges remaining to be faced to originate iPSC in a reliable fashion and with the quality required for safe clinical applications. In addition, reprogramming raises the possibility for the derivation of patient-specific autologous cells for personalized therapies. Reprogrammed cells are currently an invaluable tool for in vitro disease modelling, high-throughput screens for drug discovery and toxicity tests. Although Yamanaka factors are commonly used for repro-gramming iPSC, other transcription factors, epigenetic regulators, microRNAs and/or small molecules have been shown to cooperate or substitute Yamanaka factors for the process. At present, advancements and refinements have been made to the original reprogramming procedure to circumvent some critical experimental issues, such as the delivery of the reprogramming factors with integrative vectors. iPSC also overcome ethical concerns associated to the derivation of human ESC from blastocysts. Moreover, iPSC present the advantage of being derived from somatic cells collected in a non-invasive manner, harbouring the individual’s genetic background, thus being autologous and limiting immune rejections. This novel reprogramming strategy applicable to human cells raised a great interest in the scientific and medical community, as iPSC represent an alternative source of pluripotent cells to human ESC. Additionally, iPSC which contribute to the germline have the potential to generate viable and fertile animals. Like mouse ESC, mouse iPSC have the capacity to aggregate and integrate the inner cell mass, and participate in the development of an embryo upon injection into a host blastocyst and its subsequent transfer into a foster pseudo pregnant female. Indeed, iPSC and ESC are morphologically indistinguishable, and in vitro these cells have the potential to differentiate into cells of the three germ layers (ectoderm, endoderm and mesoderm) and to originate virtually all cells of adult organisms. iPSC achieve a high degree of dedifferentiation and acquire properties similar to those of embryonic stem cells (ESC). Subsequently, the Yamanaka factors, or other combinations of factors were successfully used to reprogram a wide range of mouse or human somatic cells into iPSC. In 2006, Kazutoshi Takahashi and Shinya Yamanaka reported for the first time the reprogramming of induced pluripotent stem cells (iPSC) from mouse somatic cells by forced expression of the transcription factors Oct4, Sox2, Klf4 and c-Myc, now termed Yamanaka factors. Finally, we present some of the audacious and pioneer clinical trials in progress with iPSC-derived cells. We briefly present the efforts made by the scientific and clinical communities to create the necessary guidelines and regulations to achieve the highest quality standards in the procedures for iPSC generation, characterization and long-term preservation. We introduce the potential held by iPSC for research and development of novel health-related applications. Here, we review some of the current challenges and concerns about iPSC technology. Besides these fundamental aspects of human biology and physiology that are revealed using iPSC or iPSC-derived cells, these cells hold an immense potential for cell-based therapies, and for the discovery of new or personalized pharmacological treatments for many disorders. In addition, iPSC can be generated from somatic cells harvested from normal individuals or patients, and used as a cellular tool to unravel mechanisms of human development and to model diseases in a manner not possible before. A major advantage of human iPSC, compared to the pluripotent embryonic stem cells, is that they can be generated from virtually any embryonic or adult somatic cell type without destruction of human blastocysts. Induced pluripotent stem cells (iPSC) technology has propelled the field of stem cells biology, providing new cells to explore the molecular mechanisms of pluripotency, cancer biology and aging.
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