Meet the World’s First Baby Born With an Assist from Stem Cells

TIME

Growing human brain tissue: The organoid without a face

The Economist

Clinical trial starts to restore vision loss using gene therapy

GlobalToronto

Scientists grow a miniature artificial human liver

COSMOS magazine

derrenbrown.co.uk

A miniature artificial human liver has been grown by British scientists in a major medical breakthrough this week.

LONDON: A miniature artificial human liver has been grown by British scientists in a major medical breakthrough this week.

The organ, which is about the size of a thumbnail, was grown using stem cells in blood taken from umbilical cords.

It is hoped such mini-livers could be used to test drugs – reducing the need for animal experiments – to help repair damaged livers and eventually to produce entire organs for lifesaving transplants.

Colin McGuckin, a professor specialising in regenerative medicine, made the breakthrough with Nico Forraz at Newcastle University in northeast England.

While other scientists have created liver cells, the Newcastle team are the first to create sizeable sections of tissue from stem cells from the umbilical cord.

The pair extracted blood from the umbilical cords of newborn babies. They were then placed in a ‘bioreactor’ developed by the U.S. space agency NASA, which mimics the effects of weightlessness. This allowed the cells to multiply more quickly. Chemicals and hormones were then added to encourage the stem cells to turn into liver tissue.

“We take the stem cells from the umbilical cord blood and make small mini-livers,” said McGuckin. “We then give them to pharmaceutical companies and they can use them to test new drugs on.

“When a drug company is developing a new drug it first tests it on human cells and then tests it on animals before beginning trials on humans,” he said.

He added that: “Moving from testing on animals to humans is a massive leap and there is still a risk. But by using the mini-livers we have developed there is no need to test on animals or humans.”

The mini-livers could potentially be used like dialysis machines, buying time for a patient’s liver to repair itself or for doctors to find a replacement liver, according to the researchers.

Professor Ian Gilmore, a liver specialist at the Royal Liverpool Hospital in northwest England, said that the Newcastle team had made a “big ethical leap forward” in not requiring embryos to produce tissue.

“It is exciting because there is a real dearth of treatments available for people with liver disease,” he said.

Scientists grow 'mini human brains' from stem cells

Toronto Sun

By Kate Kelland

www.theverge.com

LONDON - 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 capitalise on the cells' innate ability to organise 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 organised 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 millimetres (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."

A close up of an organoid with retinal tissue (brown)./
www.theverge.com

Scientists Use 3-D Printer to Speed Human Embryonic Stem Cell Research

Image of human embryo stem cell droplets courtesy of Will Shu/Biofabrication

scientificamerican

By Larry Greenemeier

Every week, it seems, there’s a new breakthrough in 3-D printing that promises us the ability to (eventually) fabricate some new thing in one of those glass-walled wonder boxes. Such things have included everything from spare parts for the International Space Station above to the beef on our dinner plates to the organs inside our bodies. Although this last idea of fabricating body parts may seem the most fanciful, a team of scientists is reporting a breakthrough in 3-D printing using human embryonic stem cells that could purportedly lead to life-like bioengineered tissue and, eventually, artificial organs tailor-made for specific patients.
Researchers have been able to engineer tissue samples in the past by combining artificial scaffold-like structures and animal cells. Depositing human embryonic stem cells in cultures using a 3-D printer offers some advantages. In particular, the cells can be positioned in droplets of uniform size cheaper, faster and more easily than using manual methods. This uniformity is important for researchers trying to generate specific cell types.

Image of 3-D cell printer courtesy of Colin Hattersley

Whereas human embryonic stem cells have proved too fragile to print in the past, scientists at Scotland’s Heriot-Watt University and Roslin Cellab, a stem cell technology company, say they have developed a new technique that allowed them to deposit droplets of a consistent size containing living cells that survived the process and maintained their ability to develop into different types of mature cells. The research will be published Tuesday in the journal Biofabrication.
In the 3-D printing process, generally a nozzle resembling an inkjet deposits thin layers of resin or a polymer that hardens—either naturally or after being sintered by a laser—into a particular structure. So-called “bioprinters” naturally use cells rather than plastics to create organic structures. However, this technique can damage the printed cells, so the Heriot-Watt and Roslin Cellab scientists developed a printing system driven by pneumatic pressure and controlled by the opening and closing of a microvalve. The researchers could precisely control the amount of cells dispensed by changing the nozzle diameter, the inlet air pressure or the opening time of the valve.

The scientists acknowledge that other researchers have in the past printed mouse embryonic stem cells and even certain types of human stem cells. Human embryonic stem cells, although more sensitive to physical manipulation, can generate a wider variety of specific cell types than other forms of human stem cells. In addition, any tissue formed would yield better models of human biology than those formed from mouse cells.
The use of embryonic stem cells has been a source of controversy particularly in the United States. Last month the US Supreme Court ended an effort to shut down government support of human embryonic stem cell research by refusing to hear a case that challenged the legality of funding for the work by the National Institutes of Health (NIH). This means NIH-funded researchers can continue to work with the 195 new human embryonic stem cell lines the federal government has made available to them.
Despite the success reported by the Scottish scientists, 3-D-printed organs are still decades away from reality. Unlike the skin and muscle tissue that some researchers have successfully fabricated in the lab, solid organs such as the liver, kidney and heart require complex vascular structures that allow them to absorb nutrients and discard waste. Researchers at the University of Pennsylvania’s Tissue Microfabrication Laboratory, the Wake Forest Institute for Regenerative Medicine and elsewhere are developing methods for bioengineering functional vessels that could someday be used to ferry blood around 3-D-printed organs.
A more immediate benefit of 3-D printing embryonic stem cells might be the ability to make tissue samples that could be used to accurately test drug compounds for toxicity in humans, without the need for animal testing, according to the researchers.

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