Reprogramming ups mortality?

Chimeric mice generated from cells reprogrammed for pluripotency (induced pluripotent stem cells, or iPS cells) show significant health problems, pointing to further challenges that must be overcome before such cells can be used in the clinic, noted iPS researcher Shinya Yamanaka said on Saturday (June 14). Speaking at the linkurl:meeting;http://www.the-scientist.com/blog/display/54746/ of the linkurl:International Society for Stem Cell Research;http://www.the-scientist.com/blog/display/54749/

By | June 16, 2008

Chimeric mice generated from cells reprogrammed for pluripotency (induced pluripotent stem cells, or iPS cells) show significant health problems, pointing to further challenges that must be overcome before such cells can be used in the clinic, noted iPS researcher Shinya Yamanaka said on Saturday (June 14). Speaking at the linkurl:meeting;http://www.the-scientist.com/blog/display/54746/ of the linkurl:International Society for Stem Cell Research;http://www.the-scientist.com/blog/display/54749/ in Philadelphia, Yamanaka presented results from his group's experiments on three types of mouse chimeras generated from mouse iPS cells so far. One type was generated from fibroblasts using a cocktail of four retrovirally delivered transcription factors, Oct-3/4, SOX2, c-Myc, and Klf4. The second type of chimera was made without the use of c-Myc, which has been implicated in causing tumors. Finally, they also generated chimeras using iPS cells derived from linkurl:liver and stomach cells.;http://www.the-scientist.com/blog/display/54308/ Yamanaka reported that, not surprisingly, half of the mice generated with c-Myc developed tumors, most often in the thyroid. Normally, the researchers found, the expression levels of the four factors in the chimeras were silenced, but in tumors, c-Myc expression was reactivated. In contrast, only one of the c-Myc-minus chimeras out of 136 developed tumors. Tumerogenicity wasn't the only safety issue the group uncovered, Yamanaka said. Regardless of whether the animals were generated with or without c-Myc, the researchers found, chimeras derived from adult cells -- whether they be fibroblasts or liver and stomach cells -- suffered a sharply increased rate of mortality. "We don't know the cause of death in these mice," he said. (The findings are not yet published.) Gene expression profiles of iPS cells generated from stomach and liver cells suggest these cells are not fully pluripotent, Yamanaka said. "This kind of partial reprogramming may be the cause of mortality." "In order to translate this technology to the clinic, we really have to understand the cause of this higher mortality," Yamanaka said, "because adult human cells are the cells we want to use." Last year, Yamanaka's group was the first to linkurl:reprogram human fibroblasts;http://www.the-scientist.com/blog/display/53873/ into pluripotent stem cells -- a landmark achievement that has since been replicated by several other teams and that has set off linkurl:a whirlwind of research;http://www.the-scientist.com/article/display/54672/ in the stem cell field.

Comments

Avatar of: Li Chen

Li Chen

Posts: 10

June 16, 2008

It is critical to know the limitations and risks of iPS. This will help us to build a real expectation of this technology. \n\n
Avatar of: anonymous poster

anonymous poster

Posts: 20

June 17, 2008

When President Bush's stem cell policy first came out, I wondered why scientists didn't try to isolate factors that cause dedifferentiation, instead of complaining about the policy. Fortunately, Yamanaka and Thomson focused on this approach, and came up with iPS cells.\nNow there are problems with these cells, perhaps due to retroviral vectors, absence of longevity or tumor suppressor genes, but this is no reason to give up. Let's not blame policies for lack of creativity or innovation!
Avatar of: Brian Lee

Brian Lee

Posts: 15

June 17, 2008

I'm assuming the researchers didn't just say, "it's dead" and tossed the carcass, and that there were other animals that were ill but not dead. Time for the histopaths to take a look for changes pointing toward the cause of death.
Avatar of: anonymous poster

anonymous poster

Posts: 1

June 18, 2008

While induced pluripotent stem cells (iPS) may be an important research tool, the media and political hype around iPS has not contributed to progress toward benefits for patients.\n\nMeanwhile, work in the private sector in collaboration with academic institutions, has produced an IND that is now before the FDA, for a human trial with hESC-derived oligodendrocytes to remyelinate damaged spinal chord axons. In pre-clinical experiments, hESC-derived cardiomyocytes engraft in damaged myocardium and appear to behave like native cells; hESC-derived islet cells engraft, produce the hormones of the endocrine pancreas, and appear to do so under homeostatic control; etc. \n\nThere is no evidence of teratomas from differentiated hESC-derived cells and minimal, if any, immune rejection. Neither should there be an issue of messing with embryos, since the cell lines were created before the Bush Doctrine, are free of animal material, and can reproduce to provide a supply of pluripotent progenitor cells that is, for all practical purposes, unlimited. \n\nThe strictures on hESC-based therapies in the public sector are an outrage. It is time to move on.\n\nAnd no, I have no affiliation whatsoever with any of the commercial or academic players in this field.\n

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