For The First Time Human Eggs Have Been Developed to Maturity in a Lab


For the first time, scientists have successfully taken human eggs from their earliest stages to maturity in a lab setting.

This accomplishment is set to give us new insight into how human eggs develop, and it could potentially offer a compelling new option to individuals who are at risk of fertility loss.

 

For the study, researchers at the University of Edinburgh took ovarian tissue from 10 people in their late 20s and 30s. Using various nutrients, they encouraged eggs to develop to maturity, the point at which they could be fertilised.

A total of 48 eggs reached the final stage of the process, and of those, nine reached full maturity.

Currently, individuals at risk of infertility due to radiotherapy or chemotherapy can have ovarian tissue removed ahead of treatment and re-implanted at a later date.

For young people who haven’t yet gone through puberty and aren’t yet producing eggs, this is the only option for preserving fertility, Evelyn Telfer, co-author of the research, told The Guardian.

That process raises concerns that re-implanting tissue taken prior to cancer treatment might reintroduce cancer cells into an individual’s body. The new procedure alleviates those concerns because instead of implanting tissue, the doctor would implant an embryo, according to Telfer.

Researchers still have much more work to do before this procedure could be used in practice. At the very least, it will take a number of years to ensure that the mature eggs produced are healthy.

According to the researchers, the eggs they grew developed faster than they would have in the body, which begs further investigation.

Moreover, a small cell known as a polar body grew to an unusually large size during the process, which could indicate developmental abnormalities.

The team wants to attempt to fertilise the eggs, so it can perform tests on the embryos.

Still, this is a major milestone in fertility research, and it could give new hope to those who may not have had any before.

Impact of aging on brain connections mapped in major scan study


UNIVERSITY OF EDINBURGH — Brain connections that play a key role in complex thinking skills show the poorest health with advancing age, new research suggests.

Connections supporting functions such as movement and hearing are relatively well preserved in later life, the findings show.

Scientists carrying out the most comprehensive study to date on ageing and the brain’s connections charted subtle ways in which the brain’s connections weaken with age.

Knowing how and where connections between brain cells – so-called white matter – decline as we age is important in understanding why some people’s brains and thinking skills age better than others.

Worsening brain connections as we age contribute to a decline in thinking skills, such as reasoning, memory and speed of thinking.

Researchers from the University of Edinburgh analysed brain scans from more than 3,500 people aged between 45 and 75 taking part in the UK Biobank study.

Researchers say the data will provide more valuable insights into healthy brain and mental ageing, as well as making contributions to understanding a range of diseases and conditions.

The study was published in Nature Communications journal.

Dr Simon Cox, of the University of Edinburgh’s Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), who led the study, said: “By precisely mapping which connections of the brain are most sensitive to age, and comparing different ways of measuring them, we hope to provide a reference point for future brain research in health and disease.

“This is only one of the first of many exciting brain imaging results still to come from this important national health resource.”

Professor Ian Deary, Director of CCACE, said: “Until recently, studies of brain scans with this number of people were not possible. Day by day the UK Biobank sample grows, and this will make it possible to look carefully at the environmental and genetic factors that are associated with more or less healthy brains in older age.”

Professor Paul Matthews of Imperial College London, Chair of the UK Biobank Expert Working Group, who was not involved in the study, said: “This report provides an early example of the impact that early opening of the growing UK Biobank Imaging Enhancement database for access by researchers world-wide will have.

“The large numbers of subjects in the database has enabled the group to rapidly characterise the ways in which the brain changes with age – and to do so with the confidence that large numbers of observations allow.

“This study highlights the feasibility of defining what is typical, to inform the development of quantitative MRI measures for decision making in the clinic.”

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The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology receives funding from the Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC).

UK Biobank was established by the Wellcome Trust, MRC, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. UK Biobank is hosted by the University of Manchester and supported by the NHS.

A video explanation of the research is available at: http://www.ccace.ed.ac.uk/news-events/latest

A whole organ has been grown inside an animal for the first time


Scientists have grown an important immune system organ from scratch inside a mouse, a breakthrough that could lead to alternatives to organ transplants in humans.

shutterstock_thymus

Image: Nerthuz/Shutterstock

Researchers from the University of Edinburgh in Scotland have taken a group of cells from a mouse embryo and grown them into a fully functional thymus, an immune system organ, in an adult mouse.

This is the first time a whole organ has been grown from scratch inside an animal, and the findings, which have been published in Nature Cell Biology, could pave the way for alternatives to organ transplants.

The thymus is an organ that’s found near the heart and produces T-cells, which fight infection and are critical to the immune system.

To grow the organ, the researchers first took fibroblast cells from a mouse embryo, genetically reprogrammed them and triggered their transformation into a type of cell that’s found in the thymus. To do this, they forced the fibroblast cells to express only a single gene, which isn’t normally expressed by fibroblasts. This gene lead to the production of a protein calledFOXN1, which triggered the fibroblasts to turn into thymus cells.

These cells were then mixed with some support cells and placed inside mice, where they developed into a complete thymus.

These newly grown thymuses were fully functional, and could even produce T-cells.

Clare Blackburn, a stem cell scientist at the MRC Centre for Regenerative Medicine at the University of Edinburgh who was part of the research team, told James Gallagher, a journalist for BBC News: “This was a complete surprise to us, that we were really being able to generate a fully functional and fully organised organ starting with reprogrammed cells in really a very straightforward way. This is a very exciting advance and it’s also very tantalising in terms of the wider field of regenerative medicine.”

She explained in a statement to the media:  “The ability to grow replacement organs from cells in the lab is one of the ‘holy grails’ in regenerative medicine. But the size and complexity of lab-grown organs has so far been limited. By directly reprogramming cells we’ve managed to produce an artificial cell type that, when transplanted, can form a fully organised and functional organ. This is an important first step towards the goal of generating a clinically useful artificial thymus in the lab.”

However, the thymus is an extremely simple organ, and scientists are still a long way off employing similar techniques in humans. And because the research involved stem cells from an embryo, this process in humans wouldn’t result in a perfect match for the recipient of the organ, meaning there is a chance of it being rejected. The researchers also need to make sure these cells won’t grow uncontrollably and pose a cancer risk.

Paolo de Coppi, a regenerative therapy researcher at Great Ormond Street Hospital in London, who wasn’t involved in the study, told the BBC: “Research such as this demonstrates that organ engineering could, in the future, be a substitute for transplantation … It remains to be seen whether, in the long term, cells generated using direct reprogramming will be able to maintain their specialised form and avoid problems such as tumour formation.”

But this early research could improve our understanding of the thymus and benefit patients with immune system problems, and it could one day lead to alternatives to organ transplants. The next step is trying to replicate the process with human cells.

Pushy bacteria could shed light on tumour growth.


Simulations of colonies containing about 100,000 cells showing circular and branched growth

Bacteria can colonize a vast number of surfaces in everyday life, from water pipes to teeth, spreading harmful disease in the process. Scientists had assumed that the growth of such colonies relies on bacteria being able to propel themselves towards sources of food, but a group of physicists in Scotland has now shown that colonies expand using nothing more than the simple mechanical repulsion between bacteria that takes place when they grow and bump into one another. This insight could improve our understanding of antibiotic resistance, say the researchers, and may even help in the fight against cancer.

Scientists use computer models of bacterial colonies to better understand a number of key characteristics of these ubiquitous structures. One parameter of great interest is a colony’s speed of growth because this determines how quickly disease can spread. Another important characteristic is a colony’s shape. Bacteria reproduce rapidly, which increases the possibility that they will mutate and acquire resistance to antibiotics. But reproduction requires nutrition and it is possible that the newly formed bacterium will be beaten by neighbouring cells in the race to reach the nutrients that are more abundant on the edge of the colony. The shape of the colony can dictate the outcome of that race.

According to existing models, which are based on a theory developed by biologist Ronald Fisher and mathematician Andrey Kolmogorov in the 1930s, the growth rate and shape of bacterial colonies depend on both a Brownian-motion-like diffusion of nutrients and a random but active motion on the part of the bacteria. However, these models fail to describe the behaviour of colonies growing on a surface, where bacteria are often unable to propel themselves.

Bacteria as ‘active matter’

In the latest work, Fred Farrell and colleagues at the University of Edinburgh, working with Oskar Hallatschek of the Max Planck Institute for Dynamics and Self-Organization in Göttingen, Germany, set out to establish the importance of mechanical forces in the growth of dense colonies of bacteria on solid substrates. Part of a growing number of physicists investigating “active matter” that exists far from thermal equilibrium, the team was also motivated by recent research showing that mechanical pressure can affect the growth and death rate of cells, including cancer cells.

The researchers model the evolution of non-self-propelling single-celled bacteria, starting with a single cell or a row of cells, which are surrounded by nutrients that they gradually deplete to grow and divide. Each bacterium is considered to be an elastic rod that grows along its length and which splits into two when it reaches a certain size. As it expands, the bacterium pushes against its nearest neighbours, creating movement by virtue of the elastic force between it and them.

The researchers found that this mechanical force pushes the colony outwards, allowing it to overcome surface friction. An increase in the strength of the pushing force leads to a faster growing colony. They also discovered that the shape the colony takes on as it expands depends on the ratio of the cells’ growth rate to the amount of nutrients available. When nutrition levels are low the colony forms branches to find more food, whereas with bountiful supplies the colony becomes circular, as is observed experimentally.

No diffusion needed

Contrary to the Fisher–Kolmogorov models, this behaviour was achieved without the diffusion of the bacteria and it also relied little on diffusion of the nutrients. Farrell’s colleague Bartek Waclaw points out that the results from the new model could be tested experimentally by confining a bacterial colony to 2D inside a microfluidic array and then imaging it to see how quickly it grows. Whereas the older models predict that the growth should be linear, the new one says it should either be slower than linear or exponential.

Having only two dimensions, however, the model’s utility will be limited, according to Waclaw. Although he adds that a basic 3D extension of the model does reproduce the main results. He explains that newly formed bacterial colonies can exist briefly as a single layer of cells, but colonies quickly build up successive layers. In addition, he points out, many bacteria exchange chemicals to communicate with each other and such signals are not incorporated in the current model. He says, however, that the model could mimic what happens at the early stages of the skin-cancer melanoma, which, he explains, starts out as an essentially flat colony of cells.

Looking at mutations

Waclaw adds that the group is now working on an extended version of the model that allows them to investigate directly how the mechanical properties of bacteria affect the rate of production of potentially antibiotic-resistant mutations. To do so the researchers assume that a certain fraction of the bacteria are mutant varieties and that these cells can grow a little faster than the rest. They then calculate the probability that a drug-resistant mutant cell can reach the nutrients ahead of its rivals and form a critical mass of cells.

A long-term aim of this research, says Waclaw, is to develop drugs that can control the mechanical properties of cells to lower the odds of those cells acquiring antibiotic resistance. “This is just a hypothesis,” he cautions, “but the ultimate hope is that it will one day be possible to modify mechanical interactions by applying a drug.”

Pushy bacteria could shed light on tumour growth.


Bacteria can colonize a vast number of surfaces in everyday life, from water pipes to teeth, spreading harmful disease in the process. Scientists had assumed that the growth of such colonies relies on bacteria being able to propel themselves towards sources of food, but a group of physicists in Scotland has now shown that colonies expand using nothing more than the simple mechanical repulsion between bacteria that takes place when they grow and bump into one another. This insight could improve our understanding of antibiotic resistance, say the researchers, and may even help in the fight against cancer.

Simulations of colonies containing about 100,000 cells showing circular and branched growth

Scientists use computer models of bacterial colonies to better understand a number of key characteristics of these ubiquitous structures. One parameter of great interest is a colony’s speed of growth because this determines how quickly disease can spread. Another important characteristic is a colony’s shape. Bacteria reproduce rapidly, which increases the possibility that they will mutate and acquire resistance to antibiotics. But reproduction requires nutrition and it is possible that the newly formed bacterium will be beaten by neighbouring cells in the race to reach the nutrients that are more abundant on the edge of the colony. The shape of the colony can dictate the outcome of that race.

According to existing models, which are based on a theory developed by biologist Ronald Fisher and mathematician Andrey Kolmogorov in the 1930s, the growth rate and shape of bacterial colonies depend on both a Brownian-motion-like diffusion of nutrients and a random but active motion on the part of the bacteria. However, these models fail to describe the behaviour of colonies growing on a surface, where bacteria are often unable to propel themselves.

Bacteria as ‘active matter’

In the latest work, Fred Farrell and colleagues at the University of Edinburgh, working with Oskar Hallatschek of the Max Planck Institute for Dynamics and Self-Organization in Göttingen, Germany, set out to establish the importance of mechanical forces in the growth of dense colonies of bacteria on solid substrates. Part of a growing number of physicists investigating “active matter” that exists far from thermal equilibrium, the team was also motivated by recent research showing that mechanical pressure can affect the growth and death rate of cells, including cancer cells.

The researchers model the evolution of non-self-propelling single-celled bacteria, starting with a single cell or a row of cells, which are surrounded by nutrients that they gradually deplete to grow and divide. Each bacterium is considered to be an elastic rod that grows along its length and which splits into two when it reaches a certain size. As it expands, the bacterium pushes against its nearest neighbours, creating movement by virtue of the elastic force between it and them.

The researchers found that this mechanical force pushes the colony outwards, allowing it to overcome surface friction. An increase in the strength of the pushing force leads to a faster growing colony. They also discovered that the shape the colony takes on as it expands depends on the ratio of the cells’ growth rate to the amount of nutrients available. When nutrition levels are low the colony forms branches to find more food, whereas with bountiful supplies the colony becomes circular, as is observed experimentally.

No diffusion needed

Contrary to the Fisher–Kolmogorov models, this behaviour was achieved without the diffusion of the bacteria and it also relied little on diffusion of the nutrients. Farrell’s colleague Bartek Waclaw points out that the results from the new model could be tested experimentally by confining a bacterial colony to 2D inside a microfluidic array and then imaging it to see how quickly it grows. Whereas the older models predict that the growth should be linear, the new one says it should either be slower than linear or exponential.

Having only two dimensions, however, the model’s utility will be limited, according to Waclaw. Although he adds that a basic 3D extension of the model does reproduce the main results. He explains that newly formed bacterial colonies can exist briefly as a single layer of cells, but colonies quickly build up successive layers. In addition, he points out, many bacteria exchange chemicals to communicate with each other and such signals are not incorporated in the current model. He says, however, that the model could mimic what happens at the early stages of the skin-cancer melanoma, which, he explains, starts out as an essentially flat colony of cells.

Looking at mutations

Waclaw adds that the group is now working on an extended version of the model that allows them to investigate directly how the mechanical properties of bacteria affect the rate of production of potentially antibiotic-resistant mutations. To do so the researchers assume that a certain fraction of the bacteria are mutant varieties and that these cells can grow a little faster than the rest. They then calculate the probability that a drug-resistant mutant cell can reach the nutrients ahead of its rivals and form a critical mass of cells.

A long-term aim of this research, says Waclaw, is to develop drugs that can control the mechanical properties of cells to lower the odds of those cells acquiring antibiotic resistance. “This is just a hypothesis,” he cautions, “but the ultimate hope is that it will one day be possible to modify mechanical interactions by applying a drug.”