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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 use of antibody and stem cell transplantation to successfully treat advanced leukemia
For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
Magnetic nanoparticles to simultaneously diagnose, monitor and treat
Whether it's magnetic nanoparticles (mNPs) giving an army of 'therapeutically armed' white blood cells direction to invade a deadly tumour's territory, or the use of mNPs to target specific nerve channels and induce nerve-led behaviour (such as the life-dependant thumping of our hearts), mNPs have come a long way in the past decade.
Of mice and men: Stem cells and ethical uncertainties
The recent creation of live mice from induced pluripotent stem cells (iPSCs) not only represents a remarkable scientific achievement, but also raises important issues, according to bioethicists at The Johns Hopkins University's Berman Institute of Bioethics.
NIH-funded researchers transform embryonic stem cells into human germ cells
Researchers funded in part by the National Institutes of Health have discovered how to transform human embryonic stem cells into germ cells, the embryonic cells that ultimately give rise to sperm and eggs.
Stem cell therapy may offer hope for acute lung injury
Researchers at the University of Illinois at Chicago College of Medicine have shown that adult stem cells from bone marrow can prevent acute lung injury in a mouse model of the disease.
Placental precursor stem cells require testosterone-free environment to survive
Trophoblast stem cells (TSCs), cells found in the layer of peripheral embryonic stem cells from which the placenta is formed, are thought to exhibit "immune privilege" that aids cell survivability and is potentially beneficial for cell and gene therapies.
Endocrine Society calls for expanded scope and funding for stem cell research
Stem cell research holds great promise for the treatment of millions of Americans with debilitating and possibly fatal diseases.
Experimental treatments restore partial vision to blind people
Two experimental treatments, a retinal prosthesis and fetal tissue transplant, restored some vision to people with blinding eye diseases. The findings, presented at Neuroscience 2009, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news on brain science and health, may lead to new treatments for the blind.
Scientists demonstrate link between genetic defect and brain changes in schizophrenia
Researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion - a mutation that confers the highest known genetic risk for schizophrenia - is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.
Small mechanical forces have big impact on embryonic stem cells
Applying a small mechanical force to embryonic stem cells could be a new way of coaxing them into a specific direction of differentiation, researchers at the University of Illinois report. Applications for force-directed cell differentiation include therapeutic cloning and regenerative medicine.
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