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J Mol Med (2012) 90:735745 DOI 10.1007/s00109-012-0913-0
REVIEW
Human induced pluripotent stem cellsfrom mechanisms to clinical applications
Katharina Drews & Justyna Jozefczuk &
Alessandro Prigione & James Adjaye
Received: 7 March 2012 /Revised: 3 May 2012 /Accepted: 6 May 2012 /Published online: 30 May 2012 # Springer-Verlag 2012
Abstract Human pluripotent stem cells hold great promise for basic research and regenerative medicine due to their inherent property to propagate infinitely, while maintaining the potential to differentiate into any given cell type of the human body. Since the first derivation in 1998, pluripotent human embryonic stem cells (ESCs) have been studied intensively, and although these cells provoke ethical and immune rejection concerns, translation of human ESC research into the clinics has been initiated. The generation of embryonic stem cell-like human induced pluripotent stem cells (iPSCs) from somatic cells by virus-mediated over-expression of distinct sets of reprogramming factors (OCT4, SOX2, KLF4, and c-MYC, or OCT4, SOX2, NANOG, and LIN28) in 2007 has opened up further opportunities in the field. While circumventing the major disputes associated with human ESCs, iPSCs offer the same advantages and, in addition, new perspectives for personalized
medicine. This review summarizes technical advances toward the generation of potentially clinically relevant human iPSCs. We also highlight key molecular events underlying the process of cellular reprogramming and discuss inherent features of iPSCs, including genome instability and epigenetic memory. Furthermore, we will give an overview of particular envisaged human iPSC applications and point out which improvements are yet to come and what has been achieved so far.
Keywords Human induced pluripotent stem cells . iPSCs . Human embryonic stem cells . ESCs . Mechanisms . Applications
Introduction
Human pluripotent stem cells, which have the ability to self-renew indefinitely and to form derivatives of all three embryonic germ layers, are of great value for basic research and potential applications in the clinics. Besides teratoma-derived embryonal carcinoma cells and embryonic germ cells, biomedical research has focused on human embryonic stem cells (ESCs) as the gold standard of human pluripotent stem cells ever since their derivation by Thomson et al. in 1998 [1]. However, ethical as well as immune rejection concerns are two major issues associated with the utilization of human ESCs in basic and translational research. These conflicts were...