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Human Induced Pluripotent Stem Cell Lines Show Stress Defense Mechanisms and Mitochondrial Regulation Similar to Those of Human Embryonic Stem Cells

Lookup NU author(s): Professor Lyle Armstrong, Dr Katarzyna Tilgner, Dr Gabriele Saretzki, Dr Stuart Atkinson, Professor Miodrag Stojkovic, Professor Majlinda Lako

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Abstract

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


Publication metadata

Author(s): Armstrong L, Tilgner K, Saretzki G, Atkinson SP, Stojkovic M, Moreno R, Przyborski S, Lako M

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2010

Volume: 28

Issue: 4

Pages: 661-673

Print publication date: 13/01/2010

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press, Inc.

URL: http://dx.doi.org/10.1002/stem.307

DOI: 10.1002/stem.307


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