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

19 February 2008
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.

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
UCLA stem cell scientists reprogram human skin cells into embryonic stem cells
Biology News Net |  12 February 2008
29 September 2008 - by Ben Jones 
Researchers at Massachusetts General Hospital, Boston, US, have developed a new, safer method for creating induced pluripotent stem (iPS) cells - adult cells made to behave like stem cells by inserting four key genes. Previously these genes have been delivered into cells using retroviruses, which can potentially trigger...
1 September 2008 - by Dr Rebecca Robey 
Researchers at the Harvard Stem Cell Institute in Boston, USA, have successfully transformed one type of adult cell in to another cell type in live mice, according to a study published in the journal Nature. The cells created were insulin-producing beta cells of the pancreas - the cells...
12 August 2008 - by Dr Rachael Panizzo 
Scientists at Harvard Stem Cell Institute and the University of Washington in the US have generated 10 stem cell lines from the skin of patients with specific genetic disorders, including muscular dystrophy, Parkinson's disease, Huntington's disease, juvenile diabetes and 'bubble boy disease', a rare immunodeficiency disease. The...
2 June 2008 - by Dr Charlotte Maden 
Researchers at Johns Hopkins University School of Medicine in the US have found a faster and more efficient way to reprogramme cells into embryonic-like stem cells so that they can be used to study genetic disorders such as sickle cell anaemia. The study was published in the...
6 May 2008 - by Evelyn Harvey 
Heart and blood cells can be grown from reprogrammed mouse skin cells, report University of California, Los Angeles (UCLA) researchers in the journal Stem Cells. The researchers say this is the first demonstration that stem cells from reprogrammed skin can be used to generate three types of...
4 February 2008 - by Antony Starza-Allen 
US President Bush has used his final State of the Union address to call on Congress to introduce legislation to ban human cloning and to also provide additional funding for 'ethical' stem cell research. 'On matters of science and life, we must trust in the innovative spirit...
14 January 2008 - by Katy Sinclair 
The Japanese scientist whose team was responsible for the breakthrough that enabled human skin cells to be reprogrammed to behave like stem cells, Shinya Yamanaka from Kyoto University, has estimated that stem cell treatments for some diseases could be as little as a decade away. Stem cells...
3 December 2007 - by Antony Starza-Allen 
Last week's announcement that two teams of researchers, led by Dr Shinya Yamanaka at Japan's Kyoto University and Professor James Thompson at the University of Wisconsin in the US, had managed to 'reprogram' human skin cells into what they term induced pluripotent stem (iPS) cells has re-ignited...
26 November 2007 - by Dr Jess Buxton 
Two groups of scientists have managed to 'reprogramme' skin cells, retuning them to an embryonic-like state in which they regain the potential to develop into any type of body cell. The studies, published in the journals Cell and Science, pave the way for new research aimed...
11 June 2007 - by Ailsa Stevens 
By Ailsa Taylor: Three independent research groups have reported successfully causing skin cells from adult mice to revert back to an embryonic stem cell-like state; a technique that could potentially help to resolve the ongoing ethical debate over stem cell research. Published in the journal Nature, this groundbreaking research could...
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