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Reprogramming adult epithelial cells into embryonic-like stem cells improves therapeutic safety

19 February 2008

By MacKenna Roberts

Appeared in BioNews 445

Japanese researchers announced last week that they have advanced their understanding and ability to safely 'reprogramme' adult stem cells to resemble embryonic stem cells (ES cells) without inducing tumours or harmful genetic abnormalities. The Japanese team of researchers, lead by Dr Shinya Yamanaka at Kyoto University, reprogrammed liver and stomach epithelial cells from adult mice to produce embryonic-like versatile cells which have the 'pluripotent' potential to develop into any type of body cell. The mice which were implanted with these reprogrammed cells - referred to as 'induced pluripotent stem' cells (iPS cells)- remained tumour-free six months after transplantation. The study, published in the journal Science, paves the way for new research aimed at generating patient-specific cell therapies for a range of debilitating disease.

The same team of scientists pioneered reprogramming adult mouse cells with a landmark study reported in 2006. They transformed the cells by amplification of four mouse genes identified as 'transcription factors', key to the reprogramming process - Oct3/4, Sox2, Klf4 and c-Myc. In November 2007, the team, along with an American group, led by James Thomson at the University of Wisconsin, directed human iPS cells, successfully created from skin cells, to produce brain and heart tissue.

The 'reprogramming' process, which in this study took roughly three months, relies upon retroviruses to introduce the crucial genes into the host genome and concern exists that retroviral genetic contamination might genetically impair the cell's function or activate oncogenes causing unchecked tumour growth. The full consequences of genetically altering these cells to become ES cell-like versus cultivating ES cells themselves remain unknown but opponents to the embryo destruction involved in ES cell research and 'therapeutic cloning', a technique that involves nuclear transfer, hope groundbreaking studies like these will provide an ethical alternative. Sir Ian Wilmut informed the Daily Telegraph that he will abandon nuclear transfer, which he had used to clone Dolly the Sheep, in favour of this technique.

Yet, many scientists believe ES cell research remains tantamount and should be done in tandem with such 'ethical' cell creation to expedite our scientific understanding and therapeutic advancement. They contend there remains much still to be understand and comparative studies would help gauge the safety and efficacy of iPS cells.

This study suggests that stem cells from adult epithelial cells, rather than skin fibroblasts used in the past, may be a safer starting point for cultivating regenerative tissues and organs. The study compared epithelial cell-derived to fibroblast-derived iPS cells. The liver and stomach epithelial iPS were more similar to ES cells and less likely to cause tumours in the chimeric mice grown from the cells. This is likely to be because they needed only one to four specific insertion sites using a retrovirus vector to introduce each gene compared to fibroblasts which require many more insertion sites thereby increasing the risk of retroviral integration causing tumours.

A UCLA (University of California, Los Angeles) study led by Kathrin Plath and William Lowry recently confirmed Yamanaka's research when they also successfully reprogrammed human skin cells into cells which were virtually identical in function and structure to ES cells.

SOURCES & REFERENCES
Embryo free way to make cells 'safe'
The Daily Telegraph | 14 February 2008
 
Epithelial cells made pluripotent
The Scientist | 14 February 2008
 
New progress by Kyoto Univ. iPS cell team
Daily Yomiuri | 15 February 2008
 
Biology News Net | 12 February 2008
 

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