Featured Research

from universities, journals, and other organizations

Adult Cells, Reprogrammed To Embryonic Stem Cell Like State, Treat Sickle-cell Anemia In Mice

Date:
December 7, 2007
Source:
Whitehead Institute for Biomedical Research
Summary:
This is the first proof of principle for using adult cells reprogrammed to an embryonic-stem-cell-like state, combined with gene and cell therapy, for successful disease treatment in mice. Similar "induced pluripotent stem cells" were recently derived with human cells.

Illustration of research. Mice received reprogrammed cells by tail injections.
Credit: Tom DiCesare

Mice with a human sickle-cell anemia disease trait have been treated successfully in a process that begins by directly reprogramming their own cells to an embryonic-stem-cell-like state, without the use of eggs. This is the first proof-of-principle of therapeutic application in mice of directly reprogrammed "induced pluripotent stem" (IPS) cells, which recently have been derived in mice as well as humans.

The research was carried out in the laboratory of Whitehead Member Rudolf Jaenisch. The IPS cells were derived using modifications of the approach originally discovered in 2006 by the Shinya Yamanaka laboratory at Kyoto University.

Scientists studied a therapeutic application of IPS cells with the sickle-cell anemia model mouse developed by the laboratory of Tim Townes of the University of Alabama at Birmingham. Sickle-cell anemia is a disease of the blood marrow caused by a defect in a single gene. The mouse model had been designed to include relevant human genes involved in blood production, including the defective version of that gene.

To create the IPS cells, the scientists started with cells from the skin of the diseased mice, explains lead author* Jacob Hanna, a postdoctoral researcher in the Jaenisch lab. These cells were modified by a standard lab technique employing retroviruses customized to insert genes into the cell's DNA. The inserted genes were Oct4, Sox2, Lif4 and c-Myc, known to act together as master regulators to keep cells in an embryonic-stem-cell-like state. IPS cells were selected based on their morphology and then verified to express gene markers specific to embryonic stem cells. To decrease or eliminate possible cancer in the treated mice, the c-Myc gene was removed by genetic manipulation from the IPS cells.

Next, the researchers followed a well-established protocol for differentiating embryonic stem cells into precursors of bone marrow adult stem cells, which can be transplanted into mice to generate normal blood cells. The scientists created such precursor cells from the IPS cells, replaced the defective blood-production gene in the precursor cells with a normal gene, and injected the resulting cells back into the diseased mice.

The blood of treated mice was tested with standard analyses employed for human patients. The analyses showed that the disease was corrected, with measurements of blood and kidney functions similar to those of normal mice.

"This demonstrates that IPS cells have the same potential for therapy as embryonic stem cells, without the ethical and practical issues raised in creating embryonic stem cells," says Jaenisch.

While IPS cells offer tremendous promise for regenerative medicine, scientists caution that major challenges must be overcome before medical applications can be considered. First among these is to find a better delivery system, since retroviruses bring other changes to the genome that are far too random to let loose in humans. "We need a delivery system that doesn't integrate itself into the genome," says Hanna. "Retroviruses can disrupt genes that should not be disrupted or activate genes that should not be activated."

Potential alternatives include other forms of viruses, synthesized versions of the proteins created by the four master regulator genes that are modified to enter the cell nucleus, and small molecules, Hanna says.

Despite the rapid progress being made with IPS cells, Jaenisch emphasizes that this field is very young, and that it's critical to continue full research on embryonic stem cells as well. "We wouldn't have known anything about IPS cells if we hadn't worked with embryonic stem cells," says Jaenisch. "For the foreseeable future, there will remain a continued need for embryonic stem cells as the crucial assessment tool for measuring the therapeutic potential of IPS cells."

*The research article "Treatment of Sickle-Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin" was published online in Science Express on December 6, 2007.


Story Source:

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


Cite This Page:

Whitehead Institute for Biomedical Research. "Adult Cells, Reprogrammed To Embryonic Stem Cell Like State, Treat Sickle-cell Anemia In Mice." ScienceDaily. ScienceDaily, 7 December 2007. <www.sciencedaily.com/releases/2007/12/071206145301.htm>.
Whitehead Institute for Biomedical Research. (2007, December 7). Adult Cells, Reprogrammed To Embryonic Stem Cell Like State, Treat Sickle-cell Anemia In Mice. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2007/12/071206145301.htm
Whitehead Institute for Biomedical Research. "Adult Cells, Reprogrammed To Embryonic Stem Cell Like State, Treat Sickle-cell Anemia In Mice." ScienceDaily. www.sciencedaily.com/releases/2007/12/071206145301.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
Powered by NewsLook.com
Google's Next Frontier: The Human Body

Google's Next Frontier: The Human Body

Newsy (July 27, 2014) Google is collecting genetic and molecular information to paint a picture of the perfectly healthy human. Video provided by Newsy
Powered by NewsLook.com
What's To Blame For Worst Ebola Outbreak In History?

What's To Blame For Worst Ebola Outbreak In History?

Newsy (July 27, 2014) A U.S. doctor has tested positive for the deadly Ebola virus, as the worst-ever outbreak continues to grow. Video provided by Newsy
Powered by NewsLook.com
Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. 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:
from the past week

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