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Stem cell surprise for tissue regeneration
June 25, 2009Baltimore, MD-Scientists working at the Carnegie Institution's Department of Embryology, with colleagues, have overturned previous research that identified critical genes for making muscle stem cells. It turns out that the genes that make muscle stem cells in the embryo are surprisingly not needed in adult muscle stem cells to regenerate muscles after injury. The finding challenges the current course of research into muscular dystrophy, muscle injury, and regenerative medicine, which uses stem cells for healing tissues, and it favours using age-matched stem cells for therapy. The study is published in the June 25 advance on-line edition of Nature.
Previous studies have shown that two genes Pax3 and Pax7, are essential for making the embryonic and neonatal muscle stem cells in the mouse. Lead researcher Christoph Lepper, a predoctoral fellow in Carnegie's Chen-Ming Fan's lab and a Johns Hopkins student, for the first time looked at these two genes in promoting stem cells at varying stages of muscle growth in live mice after birth.
As Christoph explained: "The paired-box genes, Pax3 and Pax7 are involved in the development of the skeletal muscles. It is well established that both genes are needed to produce muscle stem cells in the embryo. A previous student, Alice Chen, studied how these genes are turned on in embryonic muscle stem cells (also published in Nature). I thought that if they are so important in the embryo, they must be important for adult muscle stem cells. Using genetic tricks, I was able to suppress both genes in the adult muscle stem cells. I was totally surprised to find that the muscle stem cells are normal without them."
The researchers then looked at whether the same was true upon injury, after which the repair process requires muscle stem cells to make new muscles. For this, they injured the leg muscles between the knee and ankle. They were again surprised that these muscle stem cells, without the two key embryonic muscle stem cell genes, could generate muscles as well as normal muscle stem cells. They even performed a second round of injury and found that the stem cells were still active.
The scientists then wondered when these genes become unnecessary for muscle stem cells to regenerate muscles. It turned out that these embryonic genes are important to muscle stem cell creation up to the first three weeks after birth. What makes the muscle stem cells different after three weeks? The scientist believe that these two embryonic muscle stem cell genes also tell the stem cells to become quiet as the organism matures. After that time is reached, they "hand over" their jobs to a different set of genes. The researchers suggest that since the adult muscle stem cells are only activated when injury occurs (by trauma or exercise), they use a new set of genes from those used during embryonic development, which proceeds without injury. The scientists are eager to find these adult muscle stem cell genes.
"We are just beginning to learn the basics of stem cell biology, and there are many surprises," remarked Allan Spradling, director of Carnegie's Department of Embryology. "This work illustrates the importance of carrying out basic research using animal models before rushing into the clinic with half-baked therapies."
Carnegie Institution
The researchers then looked at whether the same was true upon injury, after which the repair process requires muscle stem cells to make new muscles. For this, they injured the leg muscles between the knee and ankle. They were again surprised that these muscle stem cells, without the two key embryonic muscle stem cell genes, could generate muscles as well as normal muscle stem cells. They even performed a second round of injury and found that the stem cells were still active.
The scientists then wondered when these genes become unnecessary for muscle stem cells to regenerate muscles. It turned out that these embryonic genes are important to muscle stem cell creation up to the first three weeks after birth. What makes the muscle stem cells different after three weeks? The scientist believe that these two embryonic muscle stem cell genes also tell the stem cells to become quiet as the organism matures. After that time is reached, they "hand over" their jobs to a different set of genes. The researchers suggest that since the adult muscle stem cells are only activated when injury occurs (by trauma or exercise), they use a new set of genes from those used during embryonic development, which proceeds without injury. The scientists are eager to find these adult muscle stem cell genes.
"We are just beginning to learn the basics of stem cell biology, and there are many surprises," remarked Allan Spradling, director of Carnegie's Department of Embryology. "This work illustrates the importance of carrying out basic research using animal models before rushing into the clinic with half-baked therapies."
Carnegie Institution
Stem Cells Current Events and Stem Cells News RSSFirst reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Bone Implant Offers Hope for Skull Deformities
A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?
Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure.
Paradoxical protein might prevent cancer
One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
The use of stem cells in regenerative medicine may also be detrimental for health
The use of stem cells in regenerative medicine is not always beneficial for human health, it may even be harmful according to a work done by the University of Granada and University of León. Scientists have demonstrated that transplantation of human mononuclear cells isolated from umbilical cord blood exerted a deleterious effect in rats with liver cirrhosis.
Penn Study Provides First Clear Idea of How Rare Bone Disease Progresses
An international team of scientists, led by researchers at the University of Pennsylvania School of Medicine, is taking the first step in developing a treatment for a rare genetic disorder called fibrodysplasia ossificans progressiva (FOP), in which the body's skeletal muscles and soft connective tissue turns to bone, immobilizing patients over a lifetime with a second skeleton.
Iowa State University researcher discovers key to vital DNA, protein interaction
A researcher at Iowa State University has discovered how a group of proteins from plant pathogenic bacteria interact with DNA in the plant cell, opening up the possibility for what the scientist calls a "cascade of advances."
Scientists successfully reprogram blood cells
Researchers have transplanted genetically modified hematopoietic stem cells into mice so that their developing red blood cells produce a critical lysosomal enzyme -preventing or reducing organ and central nervous system damage from the often-fatal genetic disorder Hurler's syndrome.
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