Researchers reverse emphysema in mice by injecting blood vessel wall cells
(Press-News.org) Researchers at Weill Cornell Medicine and NewYork-Presbyterian in New York have discovered that injecting mice with pulmonary endothelial cells--the cells that line the walls of blood vessels in the lung--can reverse the symptoms of emphysema. The study, which will be published July 21 in the Journal of Experimental Medicine (JEM), may lead to new treatments for chronic obstructive pulmonary disease (COPD), an inflammatory lung disease associated with smoking that is thought to be the third leading cause of death worldwide.
Emphysema is one of the characteristic features of COPD in which the tiny air sacs, or alveoli, within the lungs are gradually destroyed, leading to breathing difficulties and, eventually, respiratory failure. The loss of alveoli is accompanied by a remodeling of the lung's blood vessels that could indicate changes in the endothelial cells that form the blood vessel walls. Under normal circumstances, endothelial cells secrete molecules that help surrounding tissues maintain and repair themselves, but dysfunctional endothelial cells can drive various diseases, including tissue fibrosis and cancer.
"However, it is not clear whether endothelial dysfunction drives COPD pathophysiology or is simply the consequence of damaged alveolar surface area," says Dr. Augustine M.K. Choi, the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and a co-senior author of the new JEM study.
Choi and colleagues found that various markers of healthy endothelial cells were reduced in the lungs of COPD patients, as well as in laboratory mice with an induced form of emphysema. Indeed, in the lung endothelial cells of mice with emphysema, numerous genes were associated with endothelial dysfunction, including genes that promote inflammation, cell death, and vascular remodeling.
"We took these features to denote a potentially dysfunctional state that could drive the development of emphysema," says co-senior author Dr. Shahin Rafii, Chief of the Division of Regenerative Medicine, Director of the Ansary Stem Cell Institute, and the Arthur B. Belfer Professor in Genetic Medicine at Weill Cornell Medicine. "This could indicate that re-establishing a healthy vasculature--by either intravenous delivery of normal lung endothelial cells or reversing aberrant endothelial cell signaling--could encourage repair and regeneration of damaged lung tissue."
Remarkably, injecting mice with healthy lung endothelial cells reduced the alveolar destruction associated with emphysema and restored lung function. Other cell types--even endothelial cells from other tissues--failed to have any beneficial effect.
Choi and colleagues then investigated the role of leucine-rich alpha-2-glycoprotein-1 (LRG1), a cell signaling protein linked to diabetic nephropathy and various forms of cancer that the researchers found to be elevated in the lung endothelial cells of patients with COPD. Removing LRG1 from endothelial cells protected mice from the tissue destruction associated with emphysema, the researchers discovered.
"Taken together, our data strongly suggest the critical role of endothelial cell function in mediating the pathogenesis of COPD/emphysema," says co-first author Dr. Alexandra Racanelli, an Instructor in Medicine at Weill Cornell Medicine. "Targeting endothelial cell biology by administering healthy lung endothelial cells and/or inhibiting the LRG1 pathway may therefore represent strategies of immense potential for the treatment of patients with advanced COPD or emphysema."
Dr. Shu Hisata from Jichi Medical University is a co-first author. Dr. Choi is a cofounder and equity stockholder for Proterris, which develops therapeutic uses for carbon monoxide. Dr. Choi also has a use patent on CO and a patent in COPD. Dr. Rafii is the founder of and a nonpaid consultant to Angiocrine Bioscience.
Hisata et al. 2021. J. Exp. Med. https://rupress.org/jem/article-lookup/doi/10.1084/jem.20200938?PR
About Journal of Experimental Medicine
Journal of Experimental Medicine (JEM) publishes peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions on research manuscripts are made through collaborative consultation between professional scientific editors and the academic editorial board. Established in 1896, JEM is published by Rockefeller University Press, a department of The Rockefeller University in New York. For more information, visit jem.org.
Visit our Newsroom, and sign up for a weekly preview of articles to be published. Embargoed media alerts are for journalists only.
Follow JEM on Twitter at @JExpMed and @RockUPress.
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
Wearable devices can detect people's stress, according to new Washington State University research, opening potential new interventions for people with addictions.
In a paper published today, July 21, in the END ...
A landmark scientific study involving marine biologists from Greece, Turkey, Cyprus, Libya, Italy, Tunisia, the UK, the US and even Malta, documenting instances where native Mediterranean species have preyed upon two highly invasive marine fish - the Pacific red lionfish and the silver-cheeked toadfish - has just been published. Prof. Alan Deidun, coordinator of the Spot the Alien Fish citizen science campaign and resident academic within the Department of Geosciences of the Faculty of Science, is a co-author of such an extensive study.
The Pacific red lionfish (Pterois miles) and the silver-cheeked toadfish (Lagocephalus sceleratus) are amongst the most invasive of non-indigenous fish species to enter the Mediterranean in recent years, posing both ecological and socio-economic hazards. ...
SARS-CoV-2 still poses major challenges to mankind. The frequent emergence of mutant forms makes the threat posed by the virus difficult to predict. The SARS-CoV-2 variant B.1.617 circulated in India and gave rise to the Delta variant, B.1.617.2, which is now becoming dominant in many countries. Infection researchers from the German Primate Center (DPZ) - Leibniz Institute for Primate Research in Göttingen have investigated the B.1.617 variant in detail. In cell culture studies, they found that this variant can infect certain lung and intestinal cell lines more efficiently than the original ...
A high proportion of staff working in intensive care units during the COVID-19 pandemic have experienced mental health conditions, according to a new study.
In a study of 515 healthcare staff working in intensive care units (ICUs) across seven countries, the researchers found that on average 48 percent of participants showed signs of mental health conditions - depression, insomnia and post-traumatic stress disorder (PTSD). Their mental health was assessed using a detailed questionnaire and a clinical scoring system.
The team also found a 40 per cent increase in the conditions for those who spent more than six hours in personal protective equipment (PPE) over ...
At low temperatures, certain materials lose their electrical resistance and conduct electricity without any loss - this phenomenon of superconductivity has been known since 1911, but it is still not fully understood. And that is a pity, because finding a material that would still have superconducting properties even at high temperatures would probably trigger a technological revolution.
A discovery made at TU Wien (Vienna) could be an important step in this direction: A team of solid-state physicists studied an unusual material - a so-called "strange metal" made of ytterbium, rhodium and silicon. Strange metals show an unusual relationship between electrical resistance and temperature. ...
A protein involved in making cells move offers a clue to how certain types of cancer metastasize and develop into secondary tumours, according to new research from the University of Warwick.
Scientists from Warwick Medical School have demonstrated for the first time that levels of this protein can increase and decrease the movement of a cell, including cancer cells - suggesting that they could play a role in the spread of tumours.
The study is published today (21 July) in the Journal of Cell Biology and was funded by the Medical Research Council, part of UK Research and Innovation.
The researchers are investigating a tiny cell component called an Intracellular nanovesicle (INV) which acts like a courier within a cell by transporting cargo to where it ...
Classical molecular sieve membranes, with 3D microparticles and 2D nanosheets as primary building blocks, are promising in chemical separation.
Separation within such membranes relies on molecular movement and transport though their intrinsic or artificial nanopores. Since the weak connections by nature between the neighboring "bricks" usually result in intercrystalline gaps in membranes, the prevailing selectivity for classical molecular sieve membranes is moderate.
Recently, a research group led by Prof. YANG Weishen and Dr. BAN Yujie from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) proposed ...
Professors at Ural Federal University (UrFU, Russia) Sergey Shcheklein and Aleksey Dubinin have developed a technology for generating energy for an electric car engine using methanol. An article describing the technology was published in the International Journal of Hydrogen Energy.
"We pour methanol into the fuel tank. An air converter, which processes methanol into a gas mixture, is installed directly inside the vehicle. A mixture or synthesis gas, consisting of hydrogen and carbon monoxide, is formed in a small volume, which is necessary for the current operation of an electric vehicle engine," said Sergey Shcheklein, head ...
According to the latest cosmological models, large spiral galaxies such as the Milky Way grew by absorbing smaller galaxies, by a sort of galactic cannibalism. Evidence for this is given by very large structures, the tidal stellar streams, which are observed around them, which are the remains of these satellite galaxies. But the full histories of the majority of these cases are hard to study, because these flows of stars are very faint, and only the remains of the most recent mergers have been detected.
A study led by the Instituto de Astrofísica de Andalucía (IAA-CSIC), with the participation of the Instituto de Astrofísica ...
Pregnancy-induced diabetes, also known as gestational diabetes, is a common metabolic complication of pregnancy. The disorder carries a significant risk of adverse obstetric outcome. Additionally, it is associated with a high risk of recurrence, progression to maternal type 2 diabetes as well as an elevated risk of obesity in foetuses exposed to hyperglycaemia during gestation.
The mechanisms causing gestational diabetes are complex and incompletely understood. The disorder has a strong underlying genetic element that interacts with lifestyle factors and the physiologic changes accompanying pregnancy to alter maternal glucose regulation.
A team of researchers from the Faculty ...
LAST 30 PRESS RELEASES:
[Press-News.org] Researchers reverse emphysema in mice by injecting blood vessel wall cells