Featured Research

from universities, journals, and other organizations

Scientists discover genetic abnormalities after creation of stem cells

Date:
March 14, 2011
Source:
Samuel Lunenfeld Research Institute
Summary:
Scientists have identified genetic abnormalities associated with reprogramming adult cells to induced pluripotent stem cells. The findings give researchers new insights into the reprogramming process, and will help make future applications of stem cell creation and subsequent use safer.

Dr. Andras Nagy's laboratory at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital and Dr. Timo Otonkoski's laboratory at Biomedicum Stem Cell Center (University of Helsinki), as well as collaborators in Europe and Canada have identified genetic abnormalities associated with reprogramming adult cells to induced pluripotent stem (iPS) cells. The findings give researchers new insights into the reprogramming process, and will help make future applications of stem cell creation and subsequent use safer.

The study was published online March 2 in Nature.

The team showed that the reprogramming process for generating iPS cells (i.e., cells that can then be 'coaxed' to become a variety of cell types for use in regenerative medicine) is associated with inherent DNA damage.

This damage is detected in the form of genetic rearrangements and 'copy number variations,' which are alterations of DNA in which a region of the genome is either deleted or amplified on certain chromosomes. The variability may either be inherited, or caused by de novo mutation.

"Our analysis shows that these genetic changes are a result of the reprogramming process itself, which raises the concern that the resultant cell lines are mutant or defective," said Dr. Nagy, a Senior Investigator at the Lunenfeld. "These mutations could alter the properties of the stem cells, affecting their applications in studying degenerative conditions and screening for drugs to treat diseases. In the longer term, this discovery has important implications in the use of these cells for replacement therapies in regenerative medicine."

"Our study also highlights the need for rigorous characterization of generated iPS lines, especially since several groups are currently trying to enhance reprogramming efficiency," said Dr. Samer Hussein, a McEwen post-doctoral scientist who initiated these studies with Dr. Otonkoski, before completing them with Dr. Nagy. "For example, increasing the efficiency of reprogramming may actually reduce the quality of the cells in the long run, if genomic integrity is not accurately assessed."

The researchers used a molecular technique called single nucleotide polymorphism (SNP) analysis to study stem cell lines, and specifically to compare the number of copy number variations in both early and intermediate-stage human iPS cells with their respective parental, originating cells.

Drs. Nagy and Otonkoski and their teams found that iPS cells had more genetic abnormalities than their originating cells and embryonic stem cells. Interestingly, however, the simple process of growing the freshly generated iPS cells for a few weeks selected against the highly mutant cell lines, and thus most of the genetic abnormalities were eventually 'weeded out.'

"However, some of the mutations are beneficial for the cells and they may survive during continued growth," said Dr. Otonkoski, Director and Senior Scientist at the Biomedicum Stem Cell Center.

Stem cells have been widely touted as a source of great hope for use in regenerative medicine, as well as in the development of new drugs to prevent and treat illnesses including Parkinson's disease, spinal cord injury and macular degeneration. But techniques for generating these uniquely malleable cells have also opened a Pandora's Box of concerns and ethical quandaries. Health Canada, the U.S. Food and Drug Administration and the European Union consider stem cells to be drugs under federal legislation, and as such, subject to the same regulations.

"Our results suggest that whole genome analysis should be included as part of quality control of iPS cell lines to ensure that these cells are genetically normal after the reprogramming process, and then use them for disease studies and/or clinical applications," said Dr. Nagy.

"Rapid development of the technologies in genome-wide analyses will make this more feasible in the future," said Dr. Otonkoski. "In addition, there is a need to further explore if other methods might mitigate the amount of DNA damage generated during the generation of stem cells," both investigators agreed.

The present study received support from the Stem Cell Network of Canada, the Canadian Institutes of Health Research and Ontario Ministry of Research and Innovation (for Dr. Nagy), the McEwen Centre Fellowship program (for Dr. Hussein), and the ESTOOLS network funding from the 6th Framework Program of the European Union (for Dr. Otonkoski).


Story Source:

The above story is based on materials provided by Samuel Lunenfeld Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Samer M. Hussein, Nizar N. Batada, Sanna Vuoristo, Reagan W. Ching, Reija Autio, Elisa Närvä, Siemon Ng, Michel Sourour, Riikka Hämäläinen, Cia Olsson, Karolina Lundin, Milla Mikkola, Ras Trokovic, Michael Peitz, Oliver Brüstle, David P. Bazett-Jones, Kari Alitalo, Riitta Lahesmaa, Andras Nagy, & Timo Otonkoski. Copy number variation and selection during reprogramming to pluripotency. Nature, March 2, 2011 DOI: 10.1038/nature09871

Cite This Page:

Samuel Lunenfeld Research Institute. "Scientists discover genetic abnormalities after creation of stem cells." ScienceDaily. ScienceDaily, 14 March 2011. <www.sciencedaily.com/releases/2011/03/110302131847.htm>.
Samuel Lunenfeld Research Institute. (2011, March 14). Scientists discover genetic abnormalities after creation of stem cells. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2011/03/110302131847.htm
Samuel Lunenfeld Research Institute. "Scientists discover genetic abnormalities after creation of stem cells." ScienceDaily. www.sciencedaily.com/releases/2011/03/110302131847.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Fears Keep Guinea Hospitals Empty

Ebola Fears Keep Guinea Hospitals Empty

AP (Oct. 23, 2014) — Fears of Ebola are keeping doctors and patients alike away from hospitals in the West African nation of Guinea. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) — Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) — Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
More People Diagnosed With TB In 2013, But There's Good News

More People Diagnosed With TB In 2013, But There's Good News

Newsy (Oct. 22, 2014) — The World Health Organizations says TB numbers rose in 2013, but it's partly due to better detection and more survivors. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins