Featured Research

from universities, journals, and other organizations

Manipulating muscle stem cells to treat muscular dystrophy

Date:
October 11, 2010
Source:
Sanford-Burnham Medical Research Institute
Summary:
Under normal circumstances, adult stem cells reside in muscle tissue, where they can differentiate into a number of different cell types. After an injury (or even a tough workout), muscles are inflamed as cells and molecules flood the area to control damage and begin repairs. When called upon to replace muscle tissue damaged by injury or genetic disease, some muscle stem cells differentiate, becoming new muscle cells, while others make more stem cells. Scientists recently uncovered the molecular messengers that translate inflammatory signals into the genetic changes that tell muscle stem cells to differentiate.

Muscle tissue (purple) from a mouse model of muscular dystrophy that has been treated with anti-TNF. Infiltrating cells (green) are typical in regenerating muscle. Active muscle stem cells (orange) are committed toward the repair of damaged muscles.
Credit: Puri lab

Under normal circumstances, adult stem cells reside in muscle tissue, where they can differentiate into a number of different cell types. After an injury (or even a tough workout), muscles are inflamed as cells and molecules flood the area to control damage and begin repairs. When called upon to replace muscle tissue damaged by injury or genetic disease, some muscle stem cells differentiate, becoming new muscle cells, while others make more stem cells.

At Sanford-Burnham Medical Research Institute (Sanford-Burnham), a team of scientists led by Pier Lorenzo Puri, M.D., Ph.D., recently uncovered the molecular messengers that translate inflammatory signals into the genetic changes that tell muscle stem cells to differentiate.

Writing in the October 8 issue of the journal Cell Stem Cell, Dr. Puri and colleagues reveal fundamental mechanisms that could be manipulated to enhance how muscle stem cells regenerate injured or diseased muscles. These findings could lead to new treatments for diseases like muscular dystrophy.

"This study helps us understand how muscle stem cells decipher external signals and elaborate them to turn genes on and off," explained Dr. Puri, who is also an associate faculty member at the Dulbecco Telethon Institute in Rome, Italy. "Now we're applying this information to help patients with muscular dystrophies, a group of genetic diseases characterized by progressive muscle loss."

Dr. Puri's findings begin with an inflammatory molecule called tumor necrosis factor (TNF), which initiates a chain reaction of molecular events when it wakes up a protein called p38 alpha MAPK. This protein is known to play a role in many processes, but here Dr. Puri and his colleagues show that TNF tells p38 alpha MAPK to enter the nucleus, where it keeps a damper on the part of the genome that defines the identity of muscle cells. Essentially, p38 alpha MAPK determines whether stem cells loitering in adult muscle tissue keep refreshing the pool of stem cells or differentiate into functioning muscle cells.

This new information on p38 alpha MAPK's role in muscle is important because it gives Dr. Puri's group a target to artificially dial the stem cell population up or down. In this study they used a chemical inhibitor and antibodies directed against TNF to block the p38 alpha MAPK activity specifically in stem cells, thus producing more stem cells. Anti-TNF antibodies provide a potential mechanism to generate more muscle stem cells in muscular dystrophy patients, especially since they are already FDA-approved to treat septic shock and arthritis. The team verified their discoveries in a mouse model of Duchenne muscular dystrophy.

"In muscular dystrophy patients, the pool of stem cells capable of regenerating new muscle becomes exhausted," said Dr. Puri. "Here we've found a strategy to refresh the pool by modulating p38 alpha MAPK. Since the effect of this treatment is reversible, withdrawing the drug could then force the expanded population of stem cells to repopulate muscle cells." Overall, these findings suggest that turning inflammatory signals off and on in regenerating muscles might enhance the ability of injured or diseased skeletal muscles to self-repair.

This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health, Telethon Italy, Europe's ENDOSTEM project, Association Francaise contre les Myopathies, Associazione Italiana Ricerca sul Cancro and Parent Project Onlus.


Story Source:

The above story is based on materials provided by Sanford-Burnham Medical Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Daniela Palacios, Chiara Mozzetta, Silvia Consalvi, Giuseppina Caretti, Valentina Saccone, Valentina Proserpio, Victor E. Marquez, Sergio Valente, Antonello Mai, Sonia V. Forcales, Vittorio Sartorelli, Pier Lorenzo Puri. TNF/p38α/Polycomb Signaling to Pax7 Locus in Satellite Cells Links Inflammation to the Epigenetic Control of Muscle Regeneration. Cell Stem Cell, Volume 7, Issue 4, 455-469, 8 October 2010 DOI: 10.1016/j.stem.2010.08.013

Cite This Page:

Sanford-Burnham Medical Research Institute. "Manipulating muscle stem cells to treat muscular dystrophy." ScienceDaily. ScienceDaily, 11 October 2010. <www.sciencedaily.com/releases/2010/10/101011223210.htm>.
Sanford-Burnham Medical Research Institute. (2010, October 11). Manipulating muscle stem cells to treat muscular dystrophy. ScienceDaily. Retrieved September 14, 2014 from www.sciencedaily.com/releases/2010/10/101011223210.htm
Sanford-Burnham Medical Research Institute. "Manipulating muscle stem cells to treat muscular dystrophy." ScienceDaily. www.sciencedaily.com/releases/2010/10/101011223210.htm (accessed September 14, 2014).

Share This



More Health & Medicine News

Sunday, September 14, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Respiratory Virus Spreads To Northeast, Now In 21 States

Respiratory Virus Spreads To Northeast, Now In 21 States

Newsy (Sep. 14, 2014) The respiratory virus Enterovirus D68, which targets children, has spread from the Midwest to 21 states. Video provided by Newsy
Powered by NewsLook.com
Shocker: Journalists Are Utterly Addicted To Coffee

Shocker: Journalists Are Utterly Addicted To Coffee

Newsy (Sep. 13, 2014) A U.K. survey found that journalists consumed the most amount of coffee, but that's only the tip of the coffee-related statistics iceberg. Video provided by Newsy
Powered by NewsLook.com
Contagious Respiratory Illness Continues to Spread Across U.S.

Contagious Respiratory Illness Continues to Spread Across U.S.

Reuters - US Online Video (Sep. 12, 2014) Hundreds of children in several states have been stricken by a serious respiratory illness that is spreading across the U.S. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Batters Sierra Leone Economy Too

Ebola Batters Sierra Leone Economy Too

Reuters - Business Video Online (Sep. 12, 2014) The World Health Organisation warns that local health workers in West Africa can't keep up with Ebola - and among those countries hardest hit by the outbreak, the economic damage is coming into focus, too. As David Pollard reports, Sierra Leone admits that growth in one of the poorest economies in the region is taking a beating. Video provided by Reuters
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