10 October 2011

Seeking superior stem cells

New technique produces one hundred-fold increase in efficiency in reprogramming human cells

A SH-iPSC Colony on STO feeders.

A SH-iPSC Colony on STO feeders. [Genome Research Limited]

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Researchers from the Wellcome Trust Sanger Institute have today (10/10/2011) announced a new technique to reprogramme human cells, such as skin cells, into stem cells. Their process increases the efficiency of cell reprogramming by one hundred-fold and generates cells of a higher quality at a faster rate.

Until now cells have been reprogrammed using four specific regulatory proteins. By adding two further regulatory factors, Liu and co-workers brought about a dramatic improvement in the efficiency of reprogramming and the robustness of stem cell development. The new streamlined process produces cells that can grow more easily.

"This research is a milestone in human stem cells," explains Wei Wang, first author on the research from the Wellcome Trust Sanger Institute. "Our technique provides a foundation to unlock the full potential of stem cells."

Stem cells are unspecialized cells that are able to renew themselves through cell division and can be induced to become functional tissue- or organ-specific cells. It is hoped that stem cells will be used to replace dying or damaged cells with healthy, functional cells. This could have wide-ranging uses in medicine such as organ replacement, bone replacement and treatment of neurodegenerative diseases.

With more than 20 years of research, gold standard stem cells are derived from mice, largely because they are easy to work with and provide accurate and reproducible results. The team's aim was to develop human cells of equivalent quality to mouse stem cells.

" Our approach will enable researchers to easily engineer and reprogramme human stem cells to generate cell types for cell replacement therapies in humans. "

Dr Pentao Liu

"The reprogrammed cells developed by our team have proved to have the same capabilities as mouse stem cells," states Pentao Liu, senior author from the Sanger Institute. "Our approach will enable researchers to easily engineer and reprogramme human stem cells to generate cell types for cell replacement therapies in humans."

Retinoic acid receptor gamma (RAR-Y) and liver receptor homolog (Lrh-1), the additional regulatory factors used by Liu and co-workers, were introduced into the skin cells along with the four other regulatory proteins. The team's technology produced reprogrammed cells after just four days, compared to the seven days required for the four-protein approach. Key indicators of successfully reprogrammed cells, Oct4 and Rex-1 genes, were seen to be switched on much faster in a much higher number of cells, demonstrating increased efficiency in reprogramming.

"This is the most promising and exciting development in our attempt to develop human stem cells that lend themselves in practical applications. It bears comparison to other technologies as it is simple, robust and reliable," says Allan Bradley, Senior Group Leader and Director Emeritus at the Sanger Institute.

Notes to Editors

Publication details

  • Rapid and efficient reprogramming of somatic cells to induced pluripotent stem cells by retinoic acid receptor gamma and liver receptor homolog 1.

    Wang W, Yang J, Liu H, Lu D, Chen X, Zenonos Z, Campos LS, Rad R, Guo G, Zhang S, Bradley A and Liu P

    Proceedings of the National Academy of Sciences of the United States of America 2011;108;45;18283-8

Funding

This work was supported by the Wellcome Trust and by the China Scholarship Council

Participating Centres

  • Wellcome Trust Sanger Institute, Hinxton, United Kingdom
  • College of Animal Science and Technology, Huazhong Agriculture University, Wuhan, China
  • Science Applications International Corporation-Frederick, Frederick
  • National Cancer Institute-Frederick, Frederick
  • Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge United Kingdom

The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.

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The Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.

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