Public Release: 

Making new muscle: Researchers in Rome produce a mouse that can regenerate its tissues

European Molecular Biology Laboratory

Rome, February 4, 2004 - Researchers at the European Molecular Biology Laboratory (EMBL) and the University of Rome "La Sapienza" have found a way to restore some of the "regenerative" ability of tissues, which happens naturally in animals at the embryonic stage of development, but is lost shortly after birth. The scientists' work, published this week in PNAS, gives new insight into how stem cells can be mobilized across the body, and how they take on specialized functions in tissue.

"Many labs have reported the integration of stem cells into various types of tissues, but on a small scale," says Prof. Nadia Rosenthal, Coordinator of EMBL's Mouse Programme in Monterotondo, Italy. "This is the first study to show that stem cells can be mobilized to achieve a major regeneration of damaged tissue."

In a collaboration with the group of Antonio Musarò at the University of Rome, the scientists investigated muscle tissue in mice, discovering that stem cells can travel large distances to reach an injury. They also found a special form of a protein called mIGF-1 induces the muscle to send the distress signal that summons them.

"This form of IGF-1 is produced in the cells of embryos, but that production shuts down quickly after birth," says Rosenthal. "It is also produced in quick bursts when muscles are injured. This made us think it might play a role in regenerating damaged tissues."

They created a strain of mouse whose muscle cells continue to produce mIGF-1 throughout its lifetime. In order to study the activity of stem cells at the injury site and to trace those cells back to their source, the authors generated a second strain of mouse whose bone marrow produced stem cells that bore a distinctive, fluorescent tag.

"mIGF-1 is acting like a megaphone," Musarò says. "If there's an injury, muscles expressing mIGF-1 send out a very loud signal, and stem cells respond from quite far away. After birth, most animals lose the signal, which may be one of the key reasons that our tissues don't regenerate as quickly when we age."

The result is a high level of muscle regeneration, which doesn't happen in normal mice that have stopped producing IGF-1. Muscle regeneration can also be boosted in aging mice, or animals with a form of muscular dystrophy, whose muscles are undergoing steady deterioration. Stem cells are recruited to the tissue and can significantly reverse the process.

This study also provides insight into how stem cells lose their generic quality and become specialized. Some researchers have maintained that upon reaching a tissue, they simply fuse to existing cells and acquire some of their characteristics.

However as Prof. Rosenthal notes, "The cells we observed went through all of the typical steps of specialisation before becoming fully integrated into the new tissue."

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About EMBL:
The European Molecular Biology Laboratory is a basic research institute funded by public research monies from 17 member states, including most of the EU, Switzerland and Israel. Research at EMBL is conducted by approximately 80 independent groups covering the spectrum of molecular biology. The Laboratory has five units: the main Laboratory in Heidelberg, and Outstations in Hinxton (the European Bioinformatics Institute), Grenoble, Hamburg, and Monterotondo near Rome. The cornerstones of EMBL's mission are: to perform basic research in molecular biology, to train scientists, students and visitors at all levels, to offer vital services to scientists in the member states, and to develop new instruments and methods in the life sciences. EMBL's international PhD Programme has a student body of about 170. The Laboratory also sponsors an active Science and Society programme. Visitors from the press and public are welcome.

About EMBL-Monterotondo:
The EMBL Mouse Biology Programme based in Monterotondo (Rome), is a recently established basic research center of excellence and innovation in mouse genetics and functional genomics, capturing new opportunities and applications of mouse genetic manipulation and becoming a hub for the international mouse research network. Alliances with other EMBL research units, neighboring facilities in the European Mutant Mouse Archive (EMMA) and Italian national research (CNR) groups, and European academic research and clinical centers has resulted in the participation of EMBL in several EU-wide initiatives to establish an international research and knowledge database, linking information on genetics/genomics, phenotyping/physiology and biomedical features. EMBL Monterotondo currently has six research groups, with a staff of close to 80 people.

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