PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Stem-cell-based strategy boosts immune system in mice

UCSF study holds promise for treatment

2013-05-16
(Press-News.org) Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, the tissue can be used to foster the development of white blood cells the body needs to mount healthy immune responses and to prevent harmful autoimmune reactions.

The scientists who developed the thymus cells — which caused the proliferation and maturation of functioning immune cells when transplanted — said the achievement marks a significant step toward potential new treatments based on stem-cell and organ transplantation, as well as new therapies for type-1 diabetes and other autoimmune diseases, and for immunodeficiency diseases.

Starting with human embryonic stem cells, UCSF researchers led by Mark Anderson, MD, PhD, an immunologist, and Matthias Hebrok, PhD, a stem-cell researcher and the director of the UCSF Diabetes Center, used a unique combination of growth factors to shape the developmental trajectory of the cells, and eventually hit upon a formula that yielded functional thymus tissue.

The result, reported in the May 16, 2013 online edition of the journal Cell Stem Cell, is functioning tissue that nurtures the growth and development of the white blood cells known as T cells. T cells are a central immune cell population that responds to specific disease pathogens and also prevents the immune system from attacking the body's own tissues.

The thymus might be a bit obscure to the layperson — it's a small gland at the top of the chest beneath the breastbone — but it is in no way expendable, as individuals with defective thymus function succumb to infection early in life.

Given the invasive nature of cell therapy, which remains completely experimental, the first treatments using laboratory-derived thymus tissue would likely be studied in patients with fatal diseases for which there are no effective treatments, Anderson said. For example, one early treatment might be for the genetic disease DeGeorge syndrome, in which some newborns are born without a thymus gland and die in infancy.

However, a potentially greater impact may be in the area of tissue transplantation, a goal of the emerging field of stem-cell-based therapies. Stem-cell-based therapies now are limited by the potential for the immune system to reject transplanted stem cells, Anderson said. For transplantation, stem cells might be coaxed down two developmental pathways simultaneously, to form both thymus tissue and a replacement organ. Transplantation of both might overcome the rejection barrier without the need for harmful immunosuppression, according to Anderson.

"The thymus is an environment in which T cells mature, and where they also are instructed on the difference between self and non-self," Anderson said. Some T cells are prepared by the thymus to attack foreign invaders — including transplants, while T cells that would attack our own tissues normally are eliminated in the thymus.

In the same vein, thymus tissue might one day be used to retrain the immune system in autoimmune diseases, in which the immune system abnormally attacks "self," thereby enhancing recognition and protecting from immune destruction.

Researchers have discovered many of the proteins and growth factors that are switched on during the course of embryonic development and that are crucial to organ formation. Hebrok has spent years trying to develop insulin-secreting beta cells, a part of the pancreas that is destroyed during the course of diabetes.

The sequential appearance of specific marker proteins within cells as they develop into the distinct organs of the gastrointestinal tract serves as a series of milestones, which has helped orient Hebrok and others as they seek to guide the formation of distinct tissues.

Hebrok likens the quest for organ specific cells, including thymus cells and the elusive pancreatic beta cell, to an adventurous road trip. The pancreas and the thymus branch off the gastrointestinal tract in different places, but they share certain developmental markers.

To get to thymus cells, the researchers tried dozens of protocols, timing the switching on of the key factors differently each time. "If we used one factor for a day longer or shorter it would not work," Hebrok said. With the milestones misplaced, "It would be like driving down the highway and missing your exit."

The researchers caution that they have not perfectly replicated the thymus, and that only about 15 percent of cells are successfully directed to become thymus tissue with the protocol used in the study.

Even so, Anderson said, "We now have developed a tool that allows us to modulate the immune system in a manner that we never had before."



INFORMATION:



Additional study authors include UCSF Diabetes Center postdoctoral fellows Audrey Parent, PhD, Holger Russ, PhD; and graduate students Imran Khan, Taylor LaFlam, and Todd Metzger.

The research was funded by the California Institute for Regenerative Medicine and by the National Institutes of Health. Mark Anderson is the Robert B. Friend and Michelle M. Friend Professor in Diabetes Research at UCSF, and Matthias Hebrok is the Hurlbut-Johnson Distinguished Professor in Diabetes Research. Hebrok and Anderson have founded a company, ThyGen Inc., to advance the discoveries described in Cell Stem Cell.

Follow UCSF
UCSF.edu | Facebook.com/ucsf | Twitter.com/ucsf | YouTube.com/ucsf



ELSE PRESS RELEASES FROM THIS DATE:

South Africa's new radio telescope reveals giant outbursts from binary star system

2013-05-16
An international team of astronomers have reported the first scientific results from the Karoo Array Telescope (KAT-7) in South Africa, the pathfinder radio telescope for the $3 billion global Square Kilometre Array (SKA) project. The results appear in the latest issue of the prestigious international astronomical journal Monthly Notices of the Royal Astronomical Society (MNRAS). Using the seven-dish KAT-7 telescope and the 26 m radio telescope at the Hartebeesthoek Radio Astronomy Observatory (HartRAO), astronomers have observed a neutron star system known as Circinus ...

Vicious cycle: Obesity sustained by changes in brain biochemistry

2013-05-16
PROVIDENCE, R.I. [Brown University] — With obesity reaching epidemic levels in some parts of the world, scientists have only begun to understand why it is such a persistent condition. A study in the Journal of Biological Chemistry adds substantially to the story by reporting the discovery of a molecular chain of events in the brains of obese rats that undermined their ability to suppress appetite and to increase calorie burning. It's a vicious cycle, involving a breakdown in how brain cells process key proteins, that allows obesity to beget further obesity. But in a finding ...

Who's your daddy?

2013-05-16
Depending on the species, males have different strategies. They may try to ensure paternity by increased surveillance and fighting off the competition, or by having more frequent sex with their long-term partners. Others react by physically punishing unfaithful females or by reducing parental care once the – potentially unrelated – offspring has arrived. Herbert Hoi and colleagues of the University of Veterinary Medicine, Vienna, together with scientists from the Slovak Academy of Sciences, Bratislava, carried out experiments with reed warblers to see how a situation of ...

Actor Johnny Depp immortalized in ancient fossil find

2013-05-16
A scientist has discovered an ancient extinct creature with 'scissor hand-like' claws in fossil records and has named it in honour of his favourite movie star. The 505 million year old fossil called Kooteninchela deppi (pronounced Koo-ten-ee-che-la depp-eye), which is a distant ancestor of lobsters and scorpions, was named after the actor Johnny Depp for his starring role as Edward Scissorhands - a movie about an artificial man named Edward, an unfinished creation, who has scissors for hands. Kooteninchela deppi is helping researchers to piece together more information ...

Carbon in a twirl: The science behind a self-assembled nano-carbon helix

2013-05-16
This news release is available in German. Nanomaterials exhibit unique properties that can only unfold when the structures of the material are very small – that is, at the nanoscale. In order to exploit these special properties such as, for example, specific quantum effects it is very important to produce predefined nanostructures in a controlled way and interpret the formation of their shape. Scientists try to understand how to initiate and control the growth of nanomaterials and are exploring different ways to design and build up nanostructures with fine control ...

Work-related stress linked to increased blood fat levels

2013-05-16
Spanish researchers have studied how job stress affects cardiovascular health. The results, published in the 'Scandinavian Journal of Public Health', link this situation to dyslipidemia, a disorder that alters the levels of lipids and lipoproteins in the blood. Experts have been saying for years that emotional stress is linked to the risk of suffering cardiovascular disease as a result of unhealthy habits such as smoking, an unsuitable diet or leading a sedentary lifestyle, among other factors. Now, a study conducted by the Sociedad de Prevención de Ibermutuamur, in ...

Study brings greater understanding of tumor growth mechanism

2013-05-16
A study led by researchers from Plymouth University Peninsula Schools of Medicine and Dentistry has for the first time revealed how the loss of a particular tumour suppressing protein leads to the abnormal growth of tumours of the brain and nervous system. The study is published in Brain: A Journal of Neurology. Tumour suppressors exist in cells to prevent abnormal cell division in our bodies. The loss of a tumour suppressor called Merlin leads to tumours in many cell types within our nervous systems. There are two copies of a tumour suppressor, one on each chromosome ...

3-D modeling technology offers groundbreaking solution for engineers

2013-05-16
Software developed at the University of Sheffield has the potential to enable engineers to make 'real world' safety assessments of structures and foundations with unprecedented ease. Developed in the Department of Civil & Structural Engineering, the software can directly identify three-dimensional collapse mechanisms and provide information about margin of safety, vitally important to engineers. A method of directly identifying two-dimensional collapse mechanisms was first developed in the Department in 2007, and commercialised through the spinout company LimitState ...

Reading the unreadable

2013-05-16
Pioneering X-ray technology is making it possible to read fragile rolled-up historical documents for the first time in centuries. Old parchment is often extremely dry and liable to crack and crumble if any attempt is made to physically unroll or unfold it. The new technology, however, eliminates the need to do so by enabling parchment to be unrolled or unfolded 'virtually' and the contents displayed on a computer screen. Developed at Cardiff University and Queen Mary, University of London with funding from the Engineering and Physical Sciences Research Council (EPSRC), ...

Paleontology: The eloquence of the otoliths

2013-05-16
Fish fossils that are about 23 million years old give unprecedented insight into the evolutionary history of the gobioid order, one of the most species-rich groups among the modern bony fishes. Researchers led by paleontologist Professor Bettina Reichenbacher from the Division of Paleontology and Geobiology at the Department of Earth and Environmental Sciences at Ludwig-Maximilians-Universitaet (LMU) in Munich / Germany have completed a comprehensive analysis of fish fossils which they assign to the group of bony fishes that includes the gobies. Their results, which have ...

LAST 30 PRESS RELEASES:

GaN-based electron beam technology from Nagoya University startup poised to overcome critical semiconductor manufacturing challenges at KIOXIA

Circle versus rectangle: Finding ‘Earth 2.0’ may be easier using a new telescope shape

Metformin changes blood metal levels in humans

Long-term anticoagulation discontinuation after catheter ablation for atrial fibrillation

Fractional flow reserve–guided complete vs culprit-only revascularization in non–ST-elevation myocardial infarction and multivessel disease

Participation of women in cardiovascular trials from 2017 to 2023

Semaglutide and tirzepatide in patients with heart failure with preserved ejection fraction

Changes in biology of internal fat may be the leading cause of heart failure

Transcatheter or surgical treatment of patients with aortic stenosis at low to intermediate risk

Promising new drug for people with stubborn high blood pressure

One shot of RSV vaccine effective against hospitalization in older adults for two seasons

Bivalent RSV prefusion F protein–based vaccine for preventing cardiovascular hospitalizations in older adults

Clonal hematopoiesis and risk of new-onset myocarditis and pericarditis

Risk of myocarditis or pericarditis with high-dose vs standard-dose influenza vaccine

High-dose vs standard-dose influenza vaccine and cardiovascular outcomes in older adults

Prevalence, determinants, and time trends of cardiovascular health in the WHO African region

New study finds that, after a heart attack, women have worse prognosis when treated with beta-blockers

CNIC-led REBOOT clinical trial challenges 40-year-old standard of care for heart attack patients

Systolic blood pressure and microaxial flow pump–associated survival in infarct-related cardiogenic shock

Beta blockers, the standard treatment after a heart attack, may offer no benefit for heart attack patients and women can have worse outcomes

High Mountain Asia’s shrinking glaciers linked to monsoon changes

All DRII-ed up: How do plants recover after drought?

Research on stigma says to just ‘shake it off’

Scientists track lightning “pollution” in real time using NASA satellite

Millions of women rely on contraceptives, but new Rice study shows they may do more than just prevent pregnancy

Hot days make for icy weather, Philippine study finds

Roxana Mehran, MD, receives the most prestigious award given by the European Society of Cardiology

World's first clinical trial showing lubiprostone aids kidney function

Capturing language change through the genes

Public trust in elections increases with clear facts

[Press-News.org] Stem-cell-based strategy boosts immune system in mice
UCSF study holds promise for treatment