Showing posts with label Cells. Show all posts
Showing posts with label Cells. Show all posts

Thursday, September 12, 2013

Scientists grow "mini human brains" from stem cells

By Kate Kelland, Health and Science Correspondent

LONDON | Wed Aug 28, 2013 1:01pm EDT

LONDON (Reuters) - Scientists have grown the first mini human brains in a laboratory and say their success could lead to new levels of understanding about the way brains develop and what goes wrong in disorders like schizophrenia and autism.

Researchers based in Austria started with human stem cells and created a culture in the lab that allowed them to grow into so-called "cerebral organoids" - or mini brains - that consisted of several distinct brain regions.

It is the first time that scientists have managed to replicate the development of brain tissue in three dimensions.

Using the organoids, the scientists were then able to produce a biological model of how a rare brain condition called microcephaly develops - suggesting the same technique could in future be used to model disorders like autism or schizophrenia that affect millions of people around the world.

"This study offers the promise of a major new tool for understanding the causes of major developmental disorders of the brain ... as well as testing possible treatments," said Paul Matthews, a professor of clinical neuroscience at Imperial College London, who was not involved in the research but was impressed with its results.

Zameel Cader, a consultant neurologist at Britain's John Radcliffe Hospital in Oxford, described the work as "fascinating and exciting". He said it extended the possibility of stem cell technologies for understanding brain development and disease mechanisms - and for discovering new drugs.

Although it starts as relatively simple tissue, the human brain swiftly develops into the most complex known natural structure, and scientists are largely in the dark about how that happens.

This makes it extremely difficult for researchers to gain an understanding of what might be going wrong in - and therefore how to treat - many common disorders of the brain such as depression, schizophrenia and autism.

GROWING STEM CELLS

To create their brain tissue, Juergen Knoblich and Madeline Lancaster at Austria's Institute of Molecular Biotechnology and fellow researchers at Britain's Edinburgh University Human Genetics Unit began with human stem cells and grew them with a special combination of nutrients designed to capitalize on the cells' innate ability to organize into complex organ structures.

They grew tissue called neuroectoderm - the layer of cells in the embryo from which all components of the brain and nervous system develop.

Fragments of this tissue were then embedded in a scaffold and put into a spinning bioreactor - a system that circulates oxygen and nutrients to allow them to grow into cerebral organoids.

After a month, the fragments had organized themselves into primitive structures that could be recognized as developing brain regions such as retina, choroid plexus and cerebral cortex, the researchers explained in a telephone briefing.

At two months, the organoids reached a maximum size of around 4 millimeters (0.16 inches), they said. Although they were very small and still a long way from resembling anything like the detailed structure of a fully developed human brain, they did contain firing neurons and distinct types of neural tissue.

"This is one of the cases where size doesn't really matter," Knoblich told reporters.

"Our system is not optimized for generation of an entire brain and that was not at all our goal. Our major goal was to analyze the development of human brain (tissue) and generate a model system we can use to transfer knowledge from animal models to a human setting."

In an early sign of how such mini brains may be useful for studying disease in the future, Knoblich's team were able to use their organoids to model the development of microcephaly, a rare neurological condition in which patients develop an abnormally small head, and identify what causes it.

Both the research team and other experts acknowledged, however, that the work was a very long way from growing a fully-functioning human brain in a laboratory.

"The human brain is the most complex thing in the known universe and has a frighteningly elaborate number of connections and interactions, both between its numerous subdivisions and the body in general," said Dean Burnett, lecturer in psychiatry at Cardiff University.

"Saying you can replicate the workings of the brain with some tissue in a dish in the lab is like inventing the first abacus and saying you can use it to run the latest version of Microsoft Windows - there is a connection there, but we're a long way from that sort of application yet."

(Editing by Mark Trevelyan)


View the original article here

Scientists grow "mini human brains" from stem cells

By Kate Kelland, Health and Science Correspondent

LONDON | Wed Aug 28, 2013 1:01pm EDT

LONDON (Reuters) - Scientists have grown the first mini human brains in a laboratory and say their success could lead to new levels of understanding about the way brains develop and what goes wrong in disorders like schizophrenia and autism.

Researchers based in Austria started with human stem cells and created a culture in the lab that allowed them to grow into so-called "cerebral organoids" - or mini brains - that consisted of several distinct brain regions.

It is the first time that scientists have managed to replicate the development of brain tissue in three dimensions.

Using the organoids, the scientists were then able to produce a biological model of how a rare brain condition called microcephaly develops - suggesting the same technique could in future be used to model disorders like autism or schizophrenia that affect millions of people around the world.

"This study offers the promise of a major new tool for understanding the causes of major developmental disorders of the brain ... as well as testing possible treatments," said Paul Matthews, a professor of clinical neuroscience at Imperial College London, who was not involved in the research but was impressed with its results.

Zameel Cader, a consultant neurologist at Britain's John Radcliffe Hospital in Oxford, described the work as "fascinating and exciting". He said it extended the possibility of stem cell technologies for understanding brain development and disease mechanisms - and for discovering new drugs.

Although it starts as relatively simple tissue, the human brain swiftly develops into the most complex known natural structure, and scientists are largely in the dark about how that happens.

This makes it extremely difficult for researchers to gain an understanding of what might be going wrong in - and therefore how to treat - many common disorders of the brain such as depression, schizophrenia and autism.

GROWING STEM CELLS

To create their brain tissue, Juergen Knoblich and Madeline Lancaster at Austria's Institute of Molecular Biotechnology and fellow researchers at Britain's Edinburgh University Human Genetics Unit began with human stem cells and grew them with a special combination of nutrients designed to capitalize on the cells' innate ability to organize into complex organ structures.

They grew tissue called neuroectoderm - the layer of cells in the embryo from which all components of the brain and nervous system develop.

Fragments of this tissue were then embedded in a scaffold and put into a spinning bioreactor - a system that circulates oxygen and nutrients to allow them to grow into cerebral organoids.

After a month, the fragments had organized themselves into primitive structures that could be recognized as developing brain regions such as retina, choroid plexus and cerebral cortex, the researchers explained in a telephone briefing.

At two months, the organoids reached a maximum size of around 4 millimeters (0.16 inches), they said. Although they were very small and still a long way from resembling anything like the detailed structure of a fully developed human brain, they did contain firing neurons and distinct types of neural tissue.

"This is one of the cases where size doesn't really matter," Knoblich told reporters.

"Our system is not optimized for generation of an entire brain and that was not at all our goal. Our major goal was to analyze the development of human brain (tissue) and generate a model system we can use to transfer knowledge from animal models to a human setting."

In an early sign of how such mini brains may be useful for studying disease in the future, Knoblich's team were able to use their organoids to model the development of microcephaly, a rare neurological condition in which patients develop an abnormally small head, and identify what causes it.

Both the research team and other experts acknowledged, however, that the work was a very long way from growing a fully-functioning human brain in a laboratory.

"The human brain is the most complex thing in the known universe and has a frighteningly elaborate number of connections and interactions, both between its numerous subdivisions and the body in general," said Dean Burnett, lecturer in psychiatry at Cardiff University.

"Saying you can replicate the workings of the brain with some tissue in a dish in the lab is like inventing the first abacus and saying you can use it to run the latest version of Microsoft Windows - there is a connection there, but we're a long way from that sort of application yet."

(Editing by Mark Trevelyan)


View the original article here

Thursday, April 18, 2013

Material screening method allows more precise control over stem cells

William Murphy, the Harvey D. Spangler professor of biomedical engineering

(Phys.org) —When it comes to delivering genes to living human tissue, the odds of success come down the molecule. The entire therapy - including the tools used to bring new genetic material into a cell - must have predictable effects.

Now, a new screening process will simplify non-viral transfection, providing a method researchers and clinicians to use to find an optimal set of biomaterials to deliver genes to cells.

Developed by William Murphy, the Harvey D. Spangler professor of biomedical engineering at the University of Wisconsin-Madison, the method gives researchers greater control over how cells react to the gene delivery mechanism. The broader implication is more nuanced, effective control over cell behavior. "We've been exploring using this concept for reprogramming of adult cells, as well as controlling differentiation of stem cell types," he says.

Murphy and his collaborators published news of their advance in the March 28, 2013 issue of Nature's Scientific Reports.

In a current successful approach, researchers use specialized viruses to deliver genetic material to cells. While efficient, that method also carries a greater risk of turning on unwanted genes or provoking an immune response from the body—making it less attractive for sensitive biomedical applications like controlling stem cell behavior, says Murphy.

His team has developed a process that does not rely on viruses. Rather, the researchers can grow specific calcium phosphate coatings that serve as a medium via which genetic material can be delivered to cells more efficiently. By matching a coating to a specific application for delivering genes, Murphy has seen up to a 70-fold increase in successful expression of those genes in human stem cells.

"From an application standpoint, the advance could be really impactful, and could enable gene delivery to become an integral part of medical device design and tissue engineering applications," says Murphy.

The process could be critical to further advances in regenerative medicine. Since researchers can apply it to any size or shape of tissue engineering structure, it could help provide engineers a simpler way to build the complex tissue structures required to deliver next-generation drug screening and patient therapies.

More information: www.nature.com/srep/2013/130328/srep01567/full/srep01567.html

Journal reference: Scientific Reports search and more info website

Provided by University of Wisconsin-Madison search and more info website


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Proper cell–cell interactions are required for the cells of early embryos to develop normally

Pulling pipettes apart to gently separate early embryonic cells. Credit: 2013 C. Lorthongpanich et al.

Some 50 years have passed since scientists first proposed the so-called 'inside–outside model' of development, which holds that the inner cells of the early embryo eventually form all the definitive structures of the fetus, whereas the outer cells give rise to the placenta. Yet, the determinants of this developmental duality have remained elusive: are lineage decisions predetermined in the egg or is cell–cell contact needed to determine cell fate?

By physically separating cells in young mouse embryos, a team led by Barbara Knowles and Davor Solter from the A*STAR Institute of Medical Biology has definitively shown that extensive cell–cell interactions are required for proper lineage commitment.

After five rounds of cell division, a fertilized egg reaches the 32-cell stage. Chanchao Lorthongpanich, a postdoctoral fellow in the Knowles–Solter laboratory, mechanically separated cells at this and prior stages and then cultured the cells individually (see image). With her colleagues, she then measured the gene expression profiles of the separated cells. They showed that the pattern was out of sync with normal development, owing to the lack of proper cell–cell contact and the associated positional information that it confers.

Each of the cells, known as blastomeres, failed to display gene markers characteristic of either the inner cell mass—the part of the embryo that gives rise to the fetus proper—or the nourishing trophectoderm, the precursor to the placenta. However, the researchers observed a tendency toward 'trophectoderm-like' expression consistent with cells receiving an 'outside' signal. Furthermore, when the researchers reassembled the cells, they could not organize themselves into the multiple tissue layers needed for proper development.

"In the absence of structure and the clues provided by it, haphazard and incoherent gene expression is coupled with loss of lineage determination," says Solter, who is now working to determine the exact cues by which cell–cell interactions lead to proper development. This process is reversible for a short time, but the subsequent loss of proper signals results in permanent damage to the blastomeres, according to Solter.

In addition to providing insights into the basic biology of mammalian development, the results could have important implications for human reproductive medicine. Currently, embryo screening techniques to test for genetic diseases require destroying one or two cells from the embryo at the eight-cell stage. Since the fate of blastomeres is determined by positional cues, rather than any predetermined fate, such diagnostic testing is unlikely to result in fetal malformation, Solter notes.

More information: Lorthongpanich, C. et al. Developmental fate and lineage commitment of singled mouse blastomeres. Development 139, 3722–3731 (2012). dev.biologists.org/content/139/20/3722.abstract

Journal reference: Development search and more info website

Provided by Agency for Science, Technology and Research (A*STAR), Singapore search and more info website


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Thursday, April 11, 2013

Podcast: A Better Sleep Drug, Spotting Cancer Cells, and the Impact of Flushed Pharmaceuticals

Have scientists developed a sleep drug without the side effects? How might a new device spot cancer cells before they metastasize? And what really happens to the drugs we flush down the toilet?

Science 's Online News Editor David Grimm chats about these stories and more with Science's Sarah Crespi.

Listen to the full Science podcast.

Read the transcript.

Hear more podcasts.


View the original article here