Researcher eliminates viral vector in stem cell reprogramming

Shinya Yamanaka MD, PhD, of Kyoto University and the Gladstone Institute of Cardiovascular Disease (GICD) has taken another step forward in improving the possibilities for the practical application of induced pluripotent stem (iPS) cell technology.

Previously, Dr. Yamanaka had shown that adult cells can be reprogrammed to become embryonic stem cell–like using a cancer-causing oncogene as one of the four genes required to reprogram the cells, and a virus to transfer the genes into the cells. In the last year, Dr. Yamanaka and other labs showed that the oncogene, c-Myc, is not needed. However the use of viruses that integrate into the genome prohibit use of iPS cells for regenerative medicine because of safety concerns: its integration into the cell's genome might activate or inactivate critical host genes.

Now Dr. Yamanaka's laboratory in Kyoto has eliminated the need for the virus. In a report published this week in Science, they showed that the critical genes can be effectively introduced without using a virus. The ability to reprogram adult cells into iPS cells without viral integration into the genome also lays to rest concerns that the reprogramming event might be dependent upon viral integration into specific genomic loci that could mediate the genetic switch.

"The iPS field and stem cell research in general is progressing rapidly," said GICD Director Deepak Srivastava, MD. "But, as Shinya has shown, each step forward reveals a new set of challenges."

Dr. Yamanka's team began this series of experiments by replacing the retrovirus with an adenoviral vector. While transfections with the genes on separate vectors didn't work, they did work when the genes were arranged in a specific order on a single vector. The same arrangement worked when the genes were incorporated into a plasmid.

To determine if the plasmid-mediated reprogrammed cells were pluripotent, the scientists transplanted the cells under the skin of immunocompromised mice. The resulting tumors contained a wide variety of cell types from all three germ layers. iPS cells injected into embryos resulted in chimeric mice with the injected cells contributing to almost all cell types.

Still, other problems remain to be solved. The efficiency of the gene transfer with the plasmid was lower than with the retrovirus. Nevertheless, this significant step moves us closer to realizing the promise of stem cells in the understanding and eventual cure of diseases.

Source: Gladstone Institutes

   

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4.8/5 after 14 votes

• CWFlink - Oct 10, 2008
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  "...adult cells can be reprogrammed to become embryonic stem cell-like..."
  
  Would all the scientists and politicians who just a few short years ago comdemned so many of us as idiots for being against "embryonic stem cell research", please stand up and admit their error? They owe many of us an appology.
  
  The greatest lesson of the history of science: often the only reason for calling someone an expert is simply because their ego demands it.
  
  We ALL have SO VERY MUCH to learn!
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• Yogaman - Oct 10, 2008
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  OK, I'm suckered in by CWFlink's somewhat defensive flame bait, so please forgive this comment not being about the article.
  
  I don't wish to call anyone an idiot, but obstructionist seems to fit anyone who was opposed to the use of discarded fertilized eggs from fertility caches or from aborted fetuses, as examples.
  
  And, because that obstructionism certainly has delayed cures and thus cost lives, would those obstructionists "please stand up and admit their error?"
  
  And is ego really the greatest lesson of the history of science? I think not. ;-)
  
  At least we can close in agreement:
  
  Given the good news for our increasingly diminishing attention spans that there remains "SO VERY MUCH to learn," as you announce, let us apply the scientific method apace!
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