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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 13 JAN 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 4, pages 661–673, April 2010
How to Cite
Armstrong, L., Tilgner, K., Saretzki, G., Atkinson, S. P., Stojkovic, M., Moreno, R., Przyborski, S. and Lako, M. (2010), Human Induced Pluripotent Stem Cell Lines Show Stress Defense Mechanisms and Mitochondrial Regulation Similar to Those of Human Embryonic Stem Cells. STEM CELLS, 28: 661–673. doi: 10.1002/stem.307
Author contributions: L.A. and M.L.: conception and design, collection and analysis of data, manuscript writing, fund raising, final approval of manuscript; K.T.: collection and assembly of data; L.A. and K.T.: contributed equally to this work; G.S.: collection and assembly of data; S.P.A.: collection and assembly of data; M.S.: manuscript writing, study design; R.M.: manuscript writing, fund raising; S.P.: collection and analysis of data.
First published online in STEM CELLS EXPRESS January 13, 2010.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue published online: 14 APR 2010
- Article first published online: 13 JAN 2010
- Manuscript Accepted: 23 DEC 2009
- Manuscript Received: 20 NOV 2009
- MRC. Grant Number: G0301182
- Newcastle University
- Conselleria de Sanidad (Generalitat Valenciana)
- Instituto de Salud Carlos III (Ministry of Science and Innovation)
- Sir James Knott Trust
- Pluripotent stem cells;
- Induced pluripotent stem cells;
The generation of induced pluripotent stem cells (iPSC) has enormous potential for the development of patient-specific regenerative medicine. Human embryonic stem cells (hESC) are able to defend their genomic integrity by maintaining low levels of reactive oxygen species (ROS) through a combination of enhanced removal capacity and limited production of these molecules. Such limited ROS production stems partly from the small number of mitochondria present in hESC; thus, it was important to determine that human iPSC (hiPSC) generation is able to eliminate the extra mitochondria present in the parental fibroblasts (reminiscent of “bottleneck” situation after fertilization) and to show that hiPSC have antioxidant defenses similar to hESC. We were able to generate seven hiPSC lines from adult human dermal fibroblasts and have fully characterized two of those clones. Both hiPSC clones express pluripotency markers and are able to differentiate in vitro into cells belonging to all three germ layers. One of these clones is able to produce fully differentiated teratoma, whereas the other hiPSC clone is unable to silence the viral expression of OCT4 and c-MYC, produce fully differentiated teratoma, and unable to downregulate the expression of some of the pluripotency genes during the differentiation process. In spite of these differences, both clones show ROS stress defense mechanisms and mitochondrial biogenesis similar to hESC. Together our data suggest that, during the reprogramming process, certain cellular mechanisms are in place to ensure that hiPSC are provided with the same defense mechanisms against accumulation of ROS as the hESC. STEM CELLS 2010;28:661–673