Making new muscle: Researchers in Rome produce a mouse that can regenerate its tissues
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 Musaṛ 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," Musaṛ 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."
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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