Harvard stem cell researchers at Massachusetts General Hospital (MGH) have taken a critical step in making possible the discovery in the relatively near future of a drug to control cystic fibrosis (CF), a fatal lung disease that claims about 500 lives each year, with 1, 000 new cases diagnosed annually. Beginning with the skin cells of patients with CF, Jayaraj Rajagopal, MD, and colleagues first created induced pluripotent stem (iPS) cells, and then used those cells to create human disease-specific functioning lung epithelium, the tissue that lines the airways and is the site of the most lethal aspect of CF, where the genes cause irreversible lung disease and inexorable respiratory failure. That tissue, which researchers now can grow in unlimited quantities in the laboratory, contains the delta-508 mutation, the gene responsible for about 70 percent of all CF cases and 90 percent of the ones in the United States.
Researchers at Boston University School of Medicine (BUSM) and Boston Medical Center (BMC) have derived a population of pure lung and thyroid progenitor cells in vitro that successfully mimic the developmental milestones of lung and thyroid tissue formation. The research, published in the journal Cell Stem Cell, identifies factors necessary for embryonic stem cells to differentiate into lung progenitor cells and provides key information about how the tissue engineering technology can be used to develop new gene and cell-based therapies to treat lung diseases. Darrell Kotton, MD, co-director of the Center for Regenerative Medicine (CReM) at Boston University and BMC and attending physician in pulmonary, allergy and sleep medicine at BMC, led this study. The findings represent years of research dedicated to identifying how to generate an unlimited source of lung progenitor cells in vitro from embryonic stem (ES) cells.
Cystic fibrosis (CF) is a devastating disease caused by mutations in the CFTR gene. In Canada, one in every 3, 600 children born has the disease. Researchers have long been puzzled as to how individuals who carry the same CFTR mutations can experience such different courses of disease. Patients with CF are affected in multiple organs such as the lungs, pancreas and liver, to varying degrees. An international team led by The Hospital for Sick Children (SickKids) and the University for Toronto (U of T) has found a potential answer to this puzzle. The team has discovered multiple genes associated with meconium ileus, a severe intestinal obstruction present at birth in 15 per cent of patients with CF. The study is published online in Nature Genetics. "Because meconium ileus is inherited, present at birth, and subject to limited environmental influence, it provides an ideal focus for identifying other contributors beyond CFTR that could result in differences in CF disease, " says the study's principal investigator Dr.
University of North Carolina at Chapel Hill researchers working as part of the International Cystic Fibrosis Consortium have discovered several regions of the genome that may predispose cystic fibrosis (CF) patients to develop an intestinal blockage while still in the uterus. A report of this international study appears online in the journal Nature Genetics. It was the work of the North America CF Gene Modifier Consortium, which brought together dozens of investigators from the United States, Canada, and from France, to identify genetic variations that could be linked with meconium ileus (MI), an intestinal obstruction that usually requires emergency surgery for treatment, and can result in a substantially increased rate of serious health problems. MI affects roughly 15-20 percent of all patients with CF, a genetic condition that causes scarring throughout the body, especially the lungs and pancreas.
ABC transporters are membrane proteins that actively pump a wealth of molecules across the membrane. Over 40 different ABC transporters perform vital functions in humans. Genetic defects in ABC transporters can trigger metabolic diseases such as gout, neonatal diabetes or cystic fibrosis, and certain ABC transporters also cause resistance to a wide range of drugs. In tumor cells, increased amounts of ABC transporters that pump chemotherapeutic substances out of the cell are often produced, thus rendering anticancer drugs ineffective. Analogous mechanisms play a key role in many pathogenic bacteria: ABC transporters carry antibiotics out of the cell - multi-resistant bacteria are the result. Despite their major importance in biology and medicine, so far the atomic structure of only a few ABC transporters has been decoded.