New Drug Could Help Prevent Artery Disease in High-risk Patients

A recent study by researchers at the University of Missouri School of Medicine has shown that a protein inhibitor drug prevents these blockages, and could be a new therapeutic approach to prevent heart attack, stroke and other diseases caused by blocked blood vessels. Dec. 21, 2016- According to the American Heart Association, approximately 2,200 Americans die each day from heart attacks, strokes and other cardiovascular diseases. The most common cause is blocked blood vessels that can no longer supply oxygen and nutrients to the heart and brain. A recent study by researchers at the University of Missouri School of Medicine has shown that a protein inhibitor drug prevents these blockages, and could be a new therapeutic approach to prevent heart attack, stroke and other diseases caused by blocked blood vessels. William Fay, MD "Arteries are living hoses that narrow and enlarge in order to regulate blood flow to organs and muscles," said William Fay, MD, the J.W. and Lois Winifred Stafford Distinguished Chair in Diabetes and Cardiovascular Research at the MU School of Medicine and senior author of the study. "Smooth muscle cells in the artery regulate blood flow by constricting and relaxing. However, when chronic inflammation occurs in a blood vessel - typically in response to diabetes, high cholesterol and cigarette smoking - the smooth muscle cells in the walls of arteries change their behavior. They gradually accumulate inside the artery and narrow the blood vessel. In the case of coronary arteries, which supply blood to heart muscle cells, this process produces blockages that can lead to a heart attack." Plasminogen activator inhibitor-1, or PAI-1, is a naturally occurring protein within blood vessels that controls cell migration. With diseases such as diabetes and obesity, [...]

Scientists find culprit responsible for calcified blood vessels in kidney disease

Stem cell finding informs research to prevent hardening of arteries By Julia Evangelou Strait September 8, 2016 A new study indicates that stem cells called Gli1 cells (shown in red) are responsible for depositing calcium in the arteries, increasing the risk of atherosclerosis. Over time, the condition can lead to cardiovascular disease and is especially common in patients with chronic kidney disease. The research may help scientists find ways to prevent hardening of arteries. (Image: Humphries Lab)Scientists have implicated a type of stem cell in the calcification of blood vessels that is common in patients with chronic kidney disease. The research will guide future studies into ways to block minerals from building up inside blood vessels and exacerbating atherosclerosis, the hardening of the arteries. The study, led by researchers at Washington University School of Medicine in St. Louis, appears Sept. 8 in the journal Cell Stem Cell. “In the past, this calcification process was viewed as passive — just mineral deposits that stick to the walls of vessels, like minerals sticking to the walls of water pipes,” said senior author Benjamin D. Humphreys, MD, PhD, director of the Division of Nephrology and an associate professor of medicine. “More recently, we’ve learned that calcification is an active process directed by cells. But there has been a lot of controversy over which cells are responsible and where they come from.” The cells implicated in clogging up blood vessels with mineral deposits live in the outer layer of arteries and are called Gli1 positive stem cells, according to the study. Because they are adult stem cells, Gli1 cells have the potential to become different types of connective tissues, including smooth muscle, fat and bone. Humphreys and his colleagues [...]

Blood-forming stem cells likely hold the key to curing many types of disease

Science Friday July 20, 2016 · 7:45 AM EDT By Adam Wernick Researchers at Stanford are reviving a technique that can use uncontaminated, blood-forming stem cells to treat a patient with cancer, autoimmune deficiency and other diseases. Beginning in the 1960s, hematopoietic, or blood-forming, stem cells became the basis for bone marrow transplants used to treat cancer patients. Then, in the 1980s and 1990s, scientists found a way to stimulate these stem cells to move from the bone marrow into the bloodstream for collection — a process called mobilization — which gradually lessened the need for bone marrow transplants. According to a 1996 study, the use of mobilized blood cells in cancer patients had multiple benefits: It led to “lower morbidity, and greater cost-effectiveness compared with conventional bone marrow transplant …and the relative ease of obtaining large amounts of stem cells made multi-cycle transplantation a viable option in the treatment of malignancies, allowing further escalation of chemotherapy dose intensity.” In 1988, Irv Weissman, a longtime stem cell researcher, developed a process that could create "purified" blood-forming stem cells from mobilized blood — that is, they could extract pure, uncomtaminated stem cells from all the other cells in the mobilized blood. This discovery became important, Weissman says, because of results found in a 1990 trial that treated women with metasticized breast cancer — cancer that has moved beyond the breast and the lymph nodes to the bones, the lung and the liver. These patients had no hope of any localized therapy to save them, but “you could give high-dose chemotherapy, and the more chemotherapy you gave the more cancer cells in the body you killed,” Weissman explains. “[But] when we looked at the mobilized blood from those women, we saw that over half of the samples [still] had breast cancer cells in [...]

Genetic error that increases risk of aortic rupture identified

Study sheds light on unexplained enlargement, weakening of aorta By Julia Evangelou Strait July 18, 2016 In young people, aortic aneurysms are most often caused by an inherited condition,such as Marfan syndrome. Standard genetic tests often pinpoint the reason for inheritedaortic disease, but some cases remain medical mysteries. A new study adds lysyl oxidaseto the standard list of genes that should be tested when a young person shows an enlarged aorta.Lysyl oxidase helps maintain structural integrity of blood vessels. (Image: Bruce Blaus) A study led by Washington University School of Medicine in St. Louis, in collaboration with Brigham and Women’s Hospital in Boston, has identified a genetic error that weakens the aorta, placing patients with this and similar errors at high risk of aortic aneurysms and ruptures. The findings will help diagnose, monitor and treat patients with aortic disease not caused by well-known conditions, such as Marfan syndrome and other genetic mutations known to disrupt connective tissues. The study appears July 18 in the Proceedings of the National Academy of Sciences. Working with the Brigham Genomic Medicine Program, the researchers identified the mutation in a family with a history of aortic disease but no known genetic reason for the condition. The error is in a gene called lysyl oxidase (LOX), which Washington University researchers have shown is responsible for connecting networks of tissue fibers that make up blood vessels. The aorta is the body’s largest artery that carries blood from the heart to the rest of the body. A lifetime of smoking and poor cardiovascular health can lead to aortic aneurysms in older adults. But bulging and tearing of the aorta in a young person is most often due to an inherited condition. A number [...]

Body’s Own Gene Editing System Generates Leukemia Stem Cells

Inhibiting the editing enzyme may provide a new therapeutic approach for blood cancers June 09, 2016  |  Heather Buschman, PhD, UCSan Diego Health Cancer stem cells are like zombies — even after a tumor is destroyed, they can keep coming back. These cells have an unlimited capacity to regenerate themselves, making more cancer stem cells and more tumors. Researchers at University of California San Diego School of Medicine have now unraveled how pre-leukemic white blood cell precursors become leukemia stem cells. The study, published June 9 in Cell Stem Cell, used human cells to define the RNA editing enzyme ADAR1’s role in leukemia, and find a way to stop it. Chronic myeloid leukemia blood cells. While DNA is like the architect’s blueprint for a cell, RNA is the like the engineer’s interpretation of the blueprint. That RNA version is frequently flawed in cancer. While many studies have uncovered pivotal DNA mutations in cancer, few have addressed the roles of RNA and mechanisms that regulate RNA. “In this study, we showed that cancer stem cells co-opt a RNA editing system to clone themselves. What’s more, we found a method to dial it down,” said senior author Catriona Jamieson, MD, PhD, associate professor of medicine and chief of the Division of Regenerative Medicine at UC San Diego School of Medicine. The enzyme at the center of this study, ADAR1, can edit the sequence of microRNAs, small pieces of genetic material. By swapping out just one microRNA building block for another, ADAR1 alters the carefully orchestrated system cells use to control which genes are turned on or off at which times. ADAR1 is known to promote cancer progression and resistance to therapy. In this study, Jamieson’s team used human blast [...]

Making bone marrow transplants safer

New approach would use antibodies rather than radiation and chemotherapy June 7, 2016 | Editor's Pick Popular  By Hannah L. Robbins, Harvard Stem Cell Institute B.D. Colen/Harvard Stem Cell Institute Communications Rahul Palchaudhuri (left), postdoctoral fellow, and David Scadden, co-director of the Harvard Stem Cell Institute, look at real-time images of blood stem cells settling into bone marrow. Harvard Stem Cell Institute (HSCI) scientists have taken the first steps toward developing a treatment that would make bone marrow blood stem cell transplantation safer, and as a result, more widely available to the millions of people living with blood disorders such as sickle cell anemia, thalassemia, andAIDS. Bone marrow transplantation is the only curative therapy for these blood diseases. But for the new, transplanted stem cells to do their work, faulty stem cells must first be “evicted” or killed. Accomplishing that requires patients to endure chemotherapy and radiation, a vicious assault on the body with lifelong consequences. In a study recently published in the journal Nature Biotechnology, HSCI researchers at Harvard University and Massachusetts General Hospital (MGH), in collaboration with Boston Children’s Hospital and Dana-Farber Cancer Institute, all Harvard affiliates, have developed a nontoxic transplantation procedure using antibodies to specifically target blood stem cells in mice, an approach they hope will make blood stem cell transplants for these patients far less toxic. The new treatment removes more than 98 percent of blood stem cells, making it as effective as chemotherapy and radiation, researchers said. “Instead of using non-targeted drugs that have lots of collateral damage, we thought we could take advantage of the precision of the immune system, in particular antibodies,” said David Scadden, co-director of HSCI, the Gerald and Darlene Jordan Professor of Medicine, and [...]

‘Step forward’ in battle against blood disorders

Belfast Telegraph April 8, 2016 British scientists have taken a first step towards mass-producing platelets - tiny cell fragments that play a vital role in blood clotting - tailored to individual patients. The team, including researchers from the NHS organisation responsible for blood transfusions, transformed stem cells into the large bone marrow cells called megakaryocytes that act as platelet factories. Hundreds of thousands of mature megakaryocytes were produced, which spontaneously began to release functional platelets. In future, the technique could lead to patients with severe injuries or blood disorders being treated with platelets made in the laboratory from their own cells. This would overcome a major problem associated with platelet donation, rejection by the recipient's immune system. Dr Cedric Ghevaert, a leading member of the team from NHS Blood and Transplant, said: "Making megakaryocytes and platelets from stem cells for transfusion has been a long-standing challenge because of the sheer numbers we need to produce to make a single unit for transfusion. "We have found a way to 'rewire' the stem cells to make them become megakaryocytes a lot faster and more efficiently. It is a major step forward towards our goal to one day make blood cells in the laboratory to transfuse to patients." Megakaryocytes, unusually large bone marrow cells, are a wonder of biology whose functioning is still not completely understood. They literally act as platelet factories, generating assembly lines for manufacturing the clotting agents along finger-like branching processes. Each megakaryocyte churns out between 5,000 and 10,000 platelets - and every adult human has nearly a trillion platelets circulating in their blood. Platelet transfusions are needed by patients with life-threatening bleeding due to major injury or surgery. They are also required by people [...]

Mount Sinai Researchers Report Insights into Blood Stem Cells from Engineered Stem Cells

Building upon previous work, researchers at the Icahn School of Medicine at Mount Sinai have identified a precursor cell in the placenta and embryo of mice that can be matured in the lab to make hematopoietic stem/progenitor cells NEW YORK, NY (PRWEB) MARCH 08, 2016 Building upon previous work, researchers at the Icahn School of Medicine at Mount Sinai identified cells in the embryos of mice that are precursors to blood stem cells or hematopoietic stem/progenitor cells (HSPCs). In previous studies, they reprogrammed mouse skin cells in the lab to become HSPCs. Now, they have identified a precursor cell in the placenta and embryo of mice that can be matured in the lab to make HSPCs. Their study, titled, "Hematopoietic Reprograming In Vitro Informs in Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells," establishes that the reprogramming process can work back and forth in blood cell development. Their results, published online today in the journal Developmental Cell, could eventually lead to a process of developing patient-specific HSPCs and more differentiated blood products for cell-replacement therapy. The need for transplantable stem cells is great for patients suffering from blood diseases such as leukemia, lymphomas, multiple myeloma and immune deficiency. Researchers are looking at ways to produce large numbers of HSPCs in the laboratory and developing methods for growing patient-specific HSPCs. The reprogramming process developed by researchers at Icahn School of Medicine at Mount Sinai appears to mimic normal blood cell creation or developmental hematopoiesis -- going from precursor cells to cells that eventually become HSPCs. This technology could potentially provide a different source of stem cells and alleviate this problem. The team analyzed mouse placentas and embryos for the presence of cells with the [...]

Researchers Identify Mechanism that Impairs Blood Flow with Aging

New findings could lead to treatments for age-related vascular disease September 8, 2015 With the world’s elderly population expected to double by 2050, understanding how aging affects the body is an important focus for researchers globally. Cardiovascular disease, the No. 1 cause of death worldwide, often is associated with aging arteries that restrict blood flow. Now, University of Missouri researchers have identified an age-related cause of arterial dysfunction, a finding that could lead to future treatments for some forms of vascular disease. “Aging affects everyone and causes changes throughout our bodies,” said Erika Boerman, PhD, a post-doctoral fellow in the Department of Medical Pharmacology and Physiology at the MU School of Medicine and lead author of the study. “The purpose of our study was to understand how blood vessels are affected by this process. We found that older arteries had a significantly lower number of sensory nerves in the tissues surrounding them and they were less sensitive to an important neurotransmitter responsible for dilation.” Boerman’s study focused on mesenteric arteries ― a type of artery that supplies blood to the small intestines ― of mice that were 4 months and 24 months old. These ages correspond to humans in their early 20s and mid-60s, respectively. Without stimulation, the diameter of the blood vessels of both younger and older mice was approximately the same. However, when stimulated to induce dilation, differences between the age groups became apparent. “The younger arteries dilated as expected,” Boerman said. “However, when we performed the same stimulation to the arteries of older mice, the vessels did not dilate. When we examined the presence of sensory nerves, we noted a 30 percent decrease in the amount surrounding the older arteries compared to [...]

SLU Researcher Opens Next Chapter on Blood-Clotting Mysteries

Grant to SLU from American Heart Association Builds on Breakthrough Research August 31, 2015 Saint Louis University Carrie Bebermeyer ST. LOUIS — Last summer, SLU scientists made a breakthrough discovery about the way in which blood clots. Through X-ray crystallography, they solved the molecular structure of prothrombin, an important blood-clotting protein, revealing an unexpected, flexible role for a “linker” region that may be the key to developing better life-saving drugs. Now, they’re racing on to solve the next puzzle. With a $214,500 grant from the American Heart Association, SLU researcher Nicola Pozzi, Ph.D., hopes to build upon these findings. “What I absolutely love about my job is the domino effect that a new discovery brings,” Pozzi said.  “When we solved the three-dimensional crystal structure of prothrombin we soon realized that our discovery would change the way we see prothrombin. “Since our results were totally unexpected, they were very challenging to interpret but at the same time very fascinating. It turned out that solving the structure was the beginning of a new unexplored chapter for prothrombin, which is full of unanswered questions. “One at a time, we hope we will address all of them. And, thanks to this award from the American Heart Association, we will be able to continue our work, test our hypothesis and eventually figure out how the transition from prothrombin to thrombin occurs at the molecular level.” The toll of cardiovascular disease Experts predict that cardiovascular disease and its blood clot-related complications, like strokes and heart attacks, are likely to remain the leading cause of death and disability, and also represent a major burden to productivity in the U.S. and worldwide, well into the year 2020. For example, ischemic stroke, which occurs when a blood [...]