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The cellular origin of fibrosis

The cellular origin of fibrosis

first_imgHarvard Stem Cell Institute scientists at Brigham and Women’s Hospital say they have found the cellular origin of the tissue scarring caused by organ damage associated with diabetes, lung disease, high blood pressure, kidney disease, and other conditions.The buildup of scar tissue, known as fibrosis, has a number of consequences, including inflammation and reduced blood and oxygen delivery to the organ. Long term, the scar tissue can lead to organ failure and sometimes eventually death. It is estimated that fibrosis contributes to 45 percent of all deaths in the developed world.The researchers, led by Benjamin Humphreys, found that in mice, a rare population of stem cells located outside of blood vessels become myofibroblast cells that secrete proteins that cause scar tissue. Killing these stem cells prevents the deadly complications of fibrosis, the researchers report today in the journal Cell Stem Cell online. Rafael Kramann, a postdoctoral fellow in Humphreys’ lab, is the first author on the paper.“Under normal circumstances, myofibroblasts stimulate wound healing, but when there’s an ongoing injury to an organ [such as the liver of a hepatitis C patient, the heart of a patient with high blood pressure, or the kidney of a patient with diabetes], these proteins clog up normal functioning,” said Humphreys, a Harvard Medical School associate professor at the Brigham, who leads the Harvard Stem Cell Institute Kidney Program.The researchers are now in discussions with a pharmaceutical firm about screening for drugs that might target and shut off these fibrosis-causing stem cells in cases of chronic organ disease. The idea of using the stem cells as targets for drug discovery began with the formation — by Humphreys, Kramann, and Derek DiRocco — of MatriTarg Laboratories, the startup that won the 2013 Harvard Deans’ Health and Life Sciences Challenge.“We wanted to know if eradication of this very small population of stem cells would improve organ function, and both kidney and heart were completely protected from developing fibrosis-related complications [such as kidney failure and heart failure],” said Humphreys, who also heads the Onco-Nephrology Program at the Dana-Farber Cancer Institute. “This provides an important proof of principle that drugs that target the stem cells could be therapeutic.”The cellular origin of kidney fibrosis has long puzzled researchers. It was unknown which kinds of stem cells form myofibroblasts, and where these stem cells are located. One long-held hypothesis was that the stem cells that give rise to myofibroblasts are found in the bone marrow, but Humphreys’ research disproves that. By tagging a specific protein called Gli1 expressed by the myofibroblast-forming stem cells, the scientists showed that the cells are found on the periphery of blood vessels, and also reside within organs.Humphreys does caution that the cell population his lab found is responsible for about 60 percent of all organ myofibroblasts, which means that they seem to be the most dominant source, but there may be other cells that also contribute to the myofibroblast population.“We haven’t disproven every hypothesis, and our results do leave room for other cells that might contribute to fibrosis,” he said.The Humphreys Lab collaborated with fellow Harvard Stem Cell Institute member Benjamin Ebert, an associate professor of medicine at Brigham and Women’s Hospital, on the work.The research was supported by the Harvard Stem Cell Institute, the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Deutsche Forschungsgemeinschaft.last_img read more

Governor Wolf: Startup Selects Northampton County as Best Location to Establish First Manufacturing Site

Governor Wolf: Startup Selects Northampton County as Best Location to Establish First Manufacturing Site

first_img Infrastructure,  Press Release Harrisburg, PA – Today, Governor Tom Wolf announced that Continental Cup Company (CCC), a manufacturer of high-end graphic paper cups, will establish its first manufacturing operation in the City of Bethlehem, Northampton County. The project will support the creation of 71 jobs in the area.“I’m proud to welcome Continental Cup Company to Pennsylvania,” said Governor Tom Wolf. “Manufacturing is thriving in the Lehigh Valley and the addition of this new facility helps to keep this momentum going.”CCC will lease a 40,000-square-foot building in Lehigh Valley Industrial Park. The company has pledged to invest at least $9.5 million into the project, which is expected to create 71 new, full-time jobs over the next three years.“We are extremely excited for our very first operation in Northampton County and proud of our contribution to the local economy providing family-sustaining jobs that will have a positive impact on Bethlehem and surrounding communities,” said Rick Timone, president of CCC. “The support from the Governor’s Action Team was a key component to making this project a reality. We appreciate Governor Wolf’s support and commitment.”CCC received a funding proposal from the Department of Community and Economic Development for a $155,000 Pennsylvania First grant, $142,000 in Job Creation Tax Credits to be to be distributed upon creation of the new jobs, and up to $31,950 in grants for workforce training and development. The company was also encouraged to apply for a low-interest $400,000 loan from the Pennsylvania Industrial Development Authority to assist with equipment costs. The project was coordinated by the Governor’s Action Team, an experienced group of economic development professionals who report directly to the governor and work with businesses that are considering locating or expanding in Pennsylvania, with additional coordination through the Lehigh Valley Economic Development Corporation (LVEDC).“Continental Cup’s move into the Lehigh Valley continues the extraordinary growth of manufacturing that is happening here,” said Don Cunningham, president and CEO of the Lehigh Valley Economic Development Corporation. “We’re grateful for the state’s support and Continental’s interest in making Northampton County its home. Continental joins the nearly 700 manufacturers in the Lehigh Valley that account for $7.4 billion of the region’s $40 billion GDP, making manufacturing our second largest sector.”CCC is a startup paper cup manufacturing company that will service the theater industry, quick service restaurants, convenience stores and food service distribution companies.For more information about the Governor’s Action Team or DCED, visit dced.pa.gov. Governor Wolf: Startup Selects Northampton County as Best Location to Establish First Manufacturing Site SHARE Email Facebook Twittercenter_img August 08, 2019last_img read more

Lambert’s goal ends Lambert’s hopes

Lambert’s goal ends Lambert’s hopes

first_img Press Association Sterling should have made it 2-0 eight minutes before the break but blew a golden chance when Lucas’ header put him clean through and he could only chip weakly at Guzan. Villa offered little going forward although the previously anonymous Tom Cleverley fired over after Ashley Westwood’s pass. It was a rare chance and the hosts were fortunate not to be further behind five minutes into the second half. They relied on Guzan as the keeper turned Skrtel’s header onto the post before he parried Henderson’s fierce drive. Carles Gil was handed his debut after signing from Valencia on the hour with Villa struggling for ideas and they almost levelled a minute later when Mignolet parried Benteke’s 10-yard volley. Borini blasted over two minutes later but Liverpool were being pinned back by a revitalised Villa as Baker headed over and then produced an air shot from just six yards. But the hosts were left to rue the misses when Rickie Lambert sealed Liverpool’s victory with 11 minutes left. Sterling received the ball on the edge of the box and he found his team-mate, whose fine touch took him away from Carlos Sanchez before he drilled into the corner. Paul Lambert’s side have won just twice in their last 18 league games and are just three points above the drop zone, while Liverpool sit seventh. Steven Gerrard failed to recover from a hamstring injury with Raheem Sterling back after his planned winter break in Jamaica. Fabian Delph made an immediate return for Villa after suspension, replacing Joe Cole, and Nathan Baker came in for the suspended Ciaran Clark. Any planned protest from Villa fans – boycotting the first eight minutes to signify eight years under chairman Randy Lerner – flopped with few taking part. They missed little, though, aside from Alan Hutton’s fine tackle to thwart the lurking Borini and Benteke heading at Simon Mignolet. Alberto Moreno did beat Brad Guzan – with a fine low shot in the 17th minute – but his celebrations were pulled back after he was correctly ruled offside. Liverpool were comfortable, patient and probing as they waited for a chance – and their persistence was rewarded on 24 minutes when Borini netted his first goal for the club since April 2013. Jordan Henderson was allowed time to cross and, after pulling away from Jores Okore, Borini volleyed in at the far post. Fabio Borini scored his first Liverpool goal in almost two years as they comfortably despatched Aston Villa 2-0 in the Barclays Premier League. Rickie Lambert clinched victory as the Reds extended their unbeaten run to eight games in all competitions. Martin Skrtel also hit the post while Christian Benteke and Nathan Baker missed decent chances for the powderpuff hosts. Villa’s goal misery continued and they have now gone eight hours and 42 minutes without scoring. last_img read more