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Lab-Grown Human ‘Mini Lungs’ Successfully Engraft in Mice, a Respiratory Research Breakthrough

Shantell M. Kirkendoll November 07, 2016 6:00 AM Scientists can now grow 3-D models of various organs from stem cells, creating new ways to study disease. More than a year ago, scientists made studying lung cells in a petri dish appear old-fashioned. A team led by University of Michigan Medical School researchers coaxed stem cells to grow into three-dimensional miniature lungs, which mimic several aspects of the structure and complexity of human lungs. Now, the researchers have transplanted the 3-D mini lungs into immunosuppressed mice and have shown that the mini lungs can survive, grow and mature. The milestone is published in the Nov. 1 issue of eLife. “In many ways, the transplanted mini lungs were indistinguishable from human adult tissue,” says senior study author Jason Spence, Ph.D., associate professor in the Department of Internal Medicine and the Department of Cell and Developmental Biology at the U-M Medical School. Respiratory diseases account for nearly 1 in 5 deaths worldwide, and lung cancer survival rates remain poor despite numerous therapeutic advances during the past 30 years. These numbers highlight the need for new, physiologically relevant models for translational lung research. Lab-grown lungs can help because they provide a human model to screen drugs, understand gene function, generate transplantable tissue and study complex human diseases, such as asthma. And they’re not the only tissues in development. As a developmental biologist, Spence has been tinkering with creating other tissues from stem cells, termed “organoids.” Researchers in the Spence Lab have had remarkable success with what some have called “intestines in a dish,” for example, which may help with the study of inflammatory bowel disease. "In just eight weeks, the resulting transplanted tissue had impressive tube-shaped airway structures similar to [...]

Gut microbes’ metabolite dampens proliferation of intestinal stem cells

Finding may provide clues to limitations of potential IBD treatment By  Tamara Bhandari June 2, 2016 Intestinal stem cells are sequestered in pockets in the lining of the intestine to avoid contact with a metabolite produced by beneficial microbes in the gut. That metabolite — butyrate — restricts the proliferation of stem cells, shown here in green, potentially hampering the intestine from repairing itself after an injury or damage related to inflammatory bowel disease, according to new research at Washington University in St. Louis. (Image: Hiroyuki Miyoshi) Intestinal stem cells are among the most rapidly dividing cells in the body, busily creating new cells to replace the ones that are constantly being sloughed off. But unlike stem cells elsewhere in the body, those in the intestine are hidden away, and for good reason, it turns out. New research at Washington University School of Medicine in St. Louis indicates stem cells are located in “pockets” in the intestine to avoid contact with a prominent metabolite produced by beneficial microbes living in the gut. That metabolite – butyrate – restricts the proliferation of stem cells, potentially hampering the intestine from repairing itself after an injury or damage resulting from inflammatory bowel disease (IBD), such as Crohn’s and colitis. The study is published June 2 in the journal Cell. The researchers showed that stem cells are normally protected from butyrate by tiny pockets built into the lining of the intestine, called the crypts of Leiberkuhn. But when the intestine is damaged, butyrate can gain access to the stem cells and inhibit their proliferation. “Scientists have known about these crypts for more than 250 years but never really understood why they existed,” said the study’s senior author Thaddeus Stappenbeck, MD, [...]

UTSW Researchers Find Molecule Able to Accelerate Tissue Regeneration Upon Injury

July 20, 2015 Patricia Silva - A study recently published in the renowned journal Science revealed a molecule able to accelerate tissue regeneration after bone marrow transplantation and other tissue injuries in mice. The study is entitled “Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration” and was led by researchers at the University of Texas Southwestern Medical Center, Case Western Reserve University and the University of Kentucky. Tissue regeneration is an important feature in several clinical settings including diseases, injury, and certain treatments such as the recovery of the hematopoietic system after bone marrow transplantation, a common treatment for leukemia patients. Because of this, there is interest in developing agents able to accelerate the tissue regeneration process, especially if they can benefit several organ systems. Researchers have now discovered a molecule that may accelerate tissue regeneration. The prostaglandin PGE2 is a signaling factor that is involved in the expansion of several types of tissue stem cells, contributing to tissue regeneration. In the study, researchers identified a prostaglandin-degrading enzyme known as 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and investigated its potential role as a negative regulator of tissue regeneration. The team used mice with depleted 15-PGDH in order to determine the role of this enzyme in controlling PGE2 levels and the tissue repair capacity in several organs. Researchers also developed a potent small-molecule inhibitor against 15-PGDH – SW033291. Researchers found that 15-PGDH–deficient mice have a twofold increase in PGE2 levels in different tissues (including bone marrow, colon and liver) in comparison to wild-type mice, an increased capability to respond to cell damage in these particular tissues, and an enhanced hematopoietic capacity. Remarkably, by inhibiting 15–PGDH with SW033291, researchers found that it was possible to rescue the damaged hematopoietic [...]

‘Bio-Artificial’ Intestine Offers New Hope for Serious Bowel Diseases

Digestive Disease Week (DDW) 2015 Luca Cicalese, MD - June 26, 2015 What if people with seriously diseased or damaged intestines could use their own stem cells to grow new "bio-artificial" intestinal tissue to replace parts of their bowels? It certainly would be a life-changing and life-saving discovery for countless children who are born with congenital conditions, such as short bowel syndrome, as well as adults suffering from injuries, tumors, or painful intestinal ailments such as Crohn disease. After nearly 10 years of work, my colleagues and I believe that we are on the verge of a major breakthrough. We have demonstrated for the first time the ability to create fully functioning "bio-artificial" tissue grown from intestinal stem cells in the bowels of laboratory rats. Our team from the University of Texas Medical Branch at Galveston presented our work to the scientific community at this year's Digestive Disease Week, the world's largest gathering of physicians and researchers in gastroenterology, hepatology, endoscopy, and gastrointestinal surgery. Other attempted cures for diseased or damaged intestines have been problematic. Intravenous feeding, although initially effective, is associated with severe complications and poor quality of life. Transplantation is potentially curative but remains challenging because of a shortage of donors, high infection rates, and potent immunosuppression due to the danger of organ rejection. Initially, we were able to create a piece of bio-artificial intestine by detaching a segment of intestine from a pig and removing all of its cells, creating a decellularized biologic scaffold. This matrix of collagen fibers was created for implanting intestinal cells from rats—and it grew into a piece of intestinal tissue. And, because our tissue scaffold came from something that already existed in nature, it was not subject to rejection by the [...]

NIH researchers reveal link between powerful gene regulatory elements and autoimmune diseases

Findings point to potential drug targets Tuesday, February 17, 2015 Investigators with the National Institutes of Health have discovered the genomic switches of a blood cell key to regulating the human immune system. The findings, published in Nature today, open the door to new research and development in drugs and personalized medicine to help those with autoimmune disorders such as inflammatory bowel disease or rheumatoid arthritis. Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system of a healthy donor. Source: National Institute of Allergy and Infectious Diseases (NIAID). The senior author of the paper, John J. O’Shea, M.D., is the scientific director at NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases. The lead author, Golnaz Vahedi, Ph.D., is a postdoctoral fellow in Dr. O’Shea’s lab in the Molecular Immunology and Inflammation Branch. The study was performed in collaboration with investigators led by NIH Director, Francis S. Collins, M.D., Ph.D., in the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute. Autoimmune diseases occur when the immune system mistakenly attacks its own cells, causing inflammation. Different tissues are affected in different diseases, for example, the joints become swollen and inflamed in rheumatoid arthritis, and the brain and spinal cord are damaged in multiple sclerosis. The causes of these diseases are not well understood, but scientists believe that they have a genetic component because they often run in families. “We now know more about the genetics of autoimmune diseases,” said NIAMS Director Stephen I. Katz, M.D., Ph.D. “Knowledge of the genetic risk factors helps us assess a person’s susceptibility to disease. With further research on the associated biological mechanisms, it could eventually enable [...]

Stem Cell Therapies for Celiac Disease and IBD Now Offered in the United States

PRWebb, by Staff ~ January 21, 2014 Regenerative Medicine Solutions (RMS), a global provider of stem cell treatments for degenerative diseases, is now offering Regenerative ColoTherapy (RCT), a proprietary stem cell treatment for people suffering with celiac and inflammatory bowel disease (IBD). Crohn’s disease and ulcerative colitis (UC) are two of the most notable conditions that fall under the IBD umbrella, affecting millions of people across the United States and the world. It is estimated that there are 1.4 million cases of Crohn’s and colitis in the United States, which roughly translates to the population size of Philadelphia. Although Crohn’s, colitis, and celiac disease are very different conditions, affecting different areas of the intestines, treatment options are similar and mainly consist of diet modification, anti-inflammatories, and immunosuppressants. In severe cases, sufferers use the restroom over 20 times a day and may require surgery to remove part of their intestine or colon. As you can imagine, symptoms of these disorders take a heavy toll on sufferer’s quality of life. Andrew, a 26-year-old RMS patient that suffers from ulcerative colitis underwent the Regenerative ColoTherapy. “For three years, I suffered from diarrhea, bleeding, painful stomach cramping, and being completely drained of energy,” Andrew said. “90 days following the RCT procedure, I noticed considerable improvements in my symptoms. My bowel movements went from upwards of 20 times a day to less than five. This procedure was invaluable and in my opinion the best option for treating this disease.” As stem cells have the ability to differentiate into many different types of tissues and have been found to be immunomodulatory and anti-inflammatory in nature, their intrinsic healing capacity is highly beneficial for sufferers of celiac disease and IBD. RMS has [...]

Research Supports Promise of Cell Therapy for Bowel Disease

Feb. 28, 2013 - by Karen Richardson WINSTON-SALEM, N.C. - Researchers at Wake Forest Baptist Medical Center and colleagues have identified a special population of adult stem cells in bone marrow that have the natural ability to migrate to the intestine and produce intestinal cells, suggesting their potential to restore healthy tissue in patients with inflammatory bowel disease (IBD). Up to 1 million Americans have IBD, which is characterized by frequent diarrhea and abdominal pain. IBD actually refers to two conditions - ulcerative colitis and Crohn's disease - in which the intestines become red and swollen and develop ulcers, probably as the result of the body having an immune response to its own tissue. While there is currently no cure for IBD, there are drug therapies aimed at reducing inflammation and preventing the immune response. Because these therapies aren't always effective, scientists hope to use stem cells to develop an injectable cell therapy to treat IBD. The research findings are reported online in the FASEB Journal (the journal of the Federation of American Societies for Experimental Biology) by senior researcher Graca Almeida-Porada, M.D., Ph.D., professor of regenerative medicine at Wake Forest Baptist's Institute for Regenerative Medicine, and colleagues. The new research complements a 2012 report by Almeida-Porada's team that identified stem cells in cord blood that are involved in blood vessel formation and also have the ability to migrate to the intestine. "We've identified two populations of human cells that migrate to the intestine - one involved in blood vessel formation and the other that can replenish intestinal cells and modulates inflammation," said Almeida-Porada. "Our hope is that a mixture of these cells could be used as an injectable therapy to treat IBD." The cells [...]