Penn Researchers Unlock Molecular Origin of Blood Stem CellsJanuary 12, 2009Implications for new blood disorder therapies PHILADELPHIA - A research team led by Nancy Speck, PhD, Professor of Cell and Developmental Biology at the University of Pennsylvania School of Medicine, has identified the location and developmental timeline in which a majority of bone marrow stem cells form in the mouse embryo. The findings, appearing online this week in the journal Nature, highlight critical steps in the origin of hematopoietic (or blood) stem cells (HSCs), says senior author Speck, who is also an Investigator with the Abramson Family Cancer Research Institute at Penn. Because HSCs, found in the bone marrow of adult mammals, generate all of the blood cell types of the body, unlocking the secrets of their origin may help researchers to better manipulate embryonic stem cells to generate new blood cells for therapy. "The ultimate goal for stem cell therapies is to take embryonic stem cells and push them down a particular lineage to replace diseased or dead cells in human adults or children," says Speck. For instance, in theory embryonic stem cells could be tweaked in a lab to provide a patient with bone marrow failure a fresh supply of compatible HSCs. To date, however, Speck says scientists have been unable to coax embryonic stem cells to become HSCs without significant genetic manipulations that are too risky for clinical therapies. First things first, Speck says: "You have to understand what's happening in the embryo." Previous studies hinted that HSCs originated from a small population of cells lining the blood vessels, called endothelial cells. But, it was unclear how endothelial cells transitioned to blood stem cells during early development. Before joining Penn in September 2008, Speck, then at Dartmouth Medical School, led a team that confirmed that HSCs in bone marrow were originating from the endothelial cells and determined whether the activity of a protein called Runx1, which is known to be critical in the formation of blood cells, was responsible for this important transition. First, the researchers inactivated the gene that codes for the protein Runx1 in the endothelial cells of mouse embryos. During development, some endothelial cells express Runx1, signaling the production of grapelike clusters of HSCs along the interior walls of several major blood vessels. Upon release from the vessel walls HSCs enter the blood circulation and travel to the fetal liver, and upon birth they relocate to the bone marrow. By selectively blocking the ability of endothelial cells to express Runx1 during embryo development, the researchers halted HSC production, demonstrating that Runx1 is vital to the endothelial cell to HSC transition. Next, Speck's team shut off Runx1 expression in mouse embryos at day 11.5 of gestation -- a time when most newly born HSCs have detached from the vessel wall and migrated to the fetal liver. The researchers found that blocking Runx1 expression had no effect on HSC formation, suggesting while Runx1 is required for the transition from endothelium to HSCs, the process is complete by the end of the 11th day of gestation. The researchers also showed that at least 95 percent of all adult HSCs (and therefore almost all adult blood) originate in the endothelium, during this short window of time during development. "This study helps illustrate a very important step in the transitional stage from embryonic stem cells to HSCs - the need to move through endothelial cells as an intermediary," Speck says. Understanding the location and developmental timeline of the origin of blood stem cells will help guide future efforts to coax embryonic stem cells to produce mature blood cells, she says. Co-authors include Michael Chen and Brandon Zeigler from Dartmouth Medical School (Departments of Biochemistry and Genetics) and Tomomasa Yokomizo and Elaine Dzierzak from Erasmus Medical Center in Rotterdam, Netherlands. This work was funded by the National Institutes of Heart, Lung and Blood and Diabetes and Digestive and Kidney Diseases The University of Pennsylvania Health System (UPHS) |
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| Related Stem Cells Current Events and Stem Cells News Articles Gene mismatch influences success of bone marrow transplants A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics. New research shows versatility of amniotic fluid stem cells For the first time, scientists have demonstrated that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought. First 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. More Stem Cells Current Events and Stem Cells News Articles |
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