̽��ֱ�� of Cambridge - regenerative medicine

Scientists find new type of cell that helps tadpoles’ tails regenerate

ta385 — Fri, 17 May 2019 08:00:00 +0000

It has long been known that some animals can regrow their tails following amputation – Aristotle observed this in the fourth century B.C. – but the mechanisms that support such regenerative potential remain poorly understood.

Using ‘single-cell genomics’, scientists at the Wellcome Trust/ Cancer Research UK Gurdon Institute at the ̽��ֱ�� of Cambridge developed an ingenious strategy to uncover what happens in different tadpole cells when they regenerate their tails.

Recent Cambridge-led advances in next-generation sequencing mean that scientists can now track which genes are turned on (being expressed) throughout a whole organism or tissue, at the resolution of individual cells. This technique, known as ‘single-cell genomics’, makes it possible to distinguish between cell types in more detail based on their characteristic selection of active genes.

These breakthroughs are beginning to reveal a map of cellular identities and lineages, as well as the factors involved in controlling how cells choose between alternative pathways during embryo development to produce the range of cell types in adults.

Using this technology, Can Aztekin and Dr Tom Hiscock – under the direction of Dr Jerome Jullien – made a detailed analysis of cell types involved in regeneration after damage in African clawed frog tadpoles (Xenopus laevis). Details are published today in the journal Science.

Dr Tom Hiscock says: “Tadpoles can regenerate their tails throughout their life; but there is a two-day period at a precise stage in development where they lose this ability. We exploited this natural phenomenon to compare the cell types present in tadpoles capable of regeneration and those no longer capable.”

̽��ֱ��researchers found that the regenerative response of stem cells is orchestrated by a single sub-population of epidermal (skin) cells, which they termed Regeneration-Organizing Cells, or ROCs.

Can Aztekin says: “It’s an astonishing process to watch unfold. After tail amputation, ROCs migrate from the body to the wound and secrete a cocktail of growth factors that coordinate the response of tissue precursor cells. These cells then work together to regenerate a tail of the right size, pattern and cell composition.”

In mammals, many tissues such as the skin epidermis, the intestinal epithelium and the blood system, undergo constant turnover through life. Cells lost through exhaustion or damage are replenished by stem cells. However, these specialised cells are usually dedicated to tissue sub-lineages, while the ability to regenerate whole organs and tissues has been lost in all but a minority of tissues such as liver and skin.

Professor Benjamin Simons, a co-author of the study says: “Understanding the mechanisms that enable some animals to regenerate whole organs represents a first step in understanding whether a similar phenomenon could be reawakened and harnessed in mammalian tissues, with implications for clinical applications.”

Reference:

C. Aztekin et al. ‘Identification of a regeneration- organizing cell in the Xenopus tail.’ Science (17 May 2019). DOI: 10.1126/science.aav9996

Researchers at the ̽��ֱ�� of Cambridge have uncovered a specialised population of skin cells that coordinate tail regeneration in frogs. These ‘Regeneration-Organizing Cells’ help to explain one of the great mysteries of nature and may offer clues about how this ability might be achieved in mammalian tissues.

It’s an astonishing process to watch unfold

Can Aztekin

Can Aztekin, Wellcome Trust Cancer Research UK Gurdon Institute, Cambridge.

Regeneration-organizing cells outline the advancing edge of a regenerating tail of a tadpole.

Acknowledgements

This research was funded by the ̽��ֱ�� of Cambridge, the Cambridge Trust and the Wellcome Trust; and supported by the European Molecular Biology Organization, the Royal Society, the European Molecular Biology Laboratory, and Cancer Research UK.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Patching up a broken heart

lw355 — Fri, 16 Jun 2017 15:00:54 +0000

When the body’s repair system kicks in, in an attempt to remove the dead heart cells, a thick layer of scar tissue begins to form. While this damage limitation process is vital to keep the heart pumping and the blood moving, the patient’s problems have really only just begun.

Cardiac scar tissue is different to the rest of the heart. It doesn’t contract or pump because it doesn’t contain any new heart muscle cells. Those that are lost at the time of the heart attack never come back. This loss of function weakens the heart and, depending on the size of the damaged area, affects both the patient’s quality of life and lifespan.

“In many patients, not only is their heart left much weaker than normal but they are unable to increase the amount of blood pumped around the body when needed during exercise,” explains Dr Sanjay Sinha. “I’ve just walked up a flight of stairs… it’s something I take for granted but many patients who’ve survived heart attacks struggle to do even basic things, like getting dressed. While there are treatments that improve the symptoms of heart failure, and some even improve survival to a limited extent, none of them tackles the underlying cause – the loss of up to a billion heart cells.”

̽��ֱ��numbers are stark. “Half a million people have heart failure in the UK. Almost half of them will not be alive in five years because of the damage to their heart. At present, the only way to really improve their heart function is to give them a heart transplant. There are only 200 heart transplants a year in the UK – it’s a drop in the ocean when many thousands need them.”

Sinha wants to mend these hearts so that they work again. “Not just by a few percent improvement but by a hundred percent.”

He leads a team of stem cell biologists in the Cambridge Stem Cell Institute. Over the past five years, with funding from the British Heart Foundation, they have been working with materials scientists Professors Ruth Cameron and Serena Best and biochemist Professor Richard Farndale on an innovative technique for growing heart patches in the laboratory – with the aim of using these to repair weakened cardiac tissue.

“In the past, people have tried injecting cardiomyocytes into damaged hearts in animal models and shown that they can restore some of the muscle that’s been lost,” says Sinha. “But even in the best possible hands, ninety percent of the cells you inject are lost because of the hostile environment.”

Instead, the Cambridge researchers are building tiny beating pieces of heart tissue in Petri dishes. ̽��ֱ��innovation that makes this possible is a scaffold. “ ̽��ֱ��idea is to make a home for heart cells that really suits them to the ground. So they can survive and thrive and function.”

̽��ֱ��scaffold is made of collagen – a highly abundant protein in the animal kingdom. Best and Cameron are experts at creating complex collagen-based structures for a variety of cell types – bone marrow, breast cancer, musculoskeletal – both as implants and as model systems to test new therapeutics.

“ ̽��ֱ��technology we’ve developed for culturing cells is exciting because it is adaptable to a huge range of applications – almost any situation where you’re trying to regenerate new tissue,” explains Best.

Best and Cameron use ‘ice-templating’ to build the scaffold. They freeze a solution of collagen, water and certain biological molecules. When the water crystals form, they push the other molecules to their boundaries. So, when the crystals are vapourised (by dropping the pressure to low levels), what’s left is a complex three-dimensional warren.

“We have immense control over this structure,” adds Cameron. “We can vary the pore structure to make cells align in certain orientations and control the ratios of cell types. We are building communities of millions of cells in an environment that resembles the heart.”

Cardiomyocytes fare better when they are surrounded by other cell types and have something to hold on to. They use proteins on their surface called integrins to touch, stick to and communicate with their environment. Farndale has perfected a ‘toolkit’ that pinpoints exactly which parts of collagen the integrins bind best; he then makes matching peptide fragments to ‘decorate’ the collagen scaffold. This gives cells a foothold in the scaffold and encourages different cell types to move in and populate the structure.

“We don’t just want a cardiac scaffold – we want it to have blood vessels and the same mechanical properties as the heart,” explains Sinha. “If it’s going to contract and function efficiently, it needs a really good blood supply. And the whole three-dimensional structure must be strong enough to survive the hostile environment of a damaged heart.”

Meanwhile, Sinha’s team pioneered the production of the different cell types needed for the patch. Their starting material is human embryonic stem cells, but they have also taken adult human cells and ‘reset’ their developmental clock. “In theory this means we can take a patient’s own cells and make patches that are identical to their own tissue. That said, millions of people are going to need this sort of therapy and so our focus at the moment is on coming up with a system where a small number of patches might be available ‘off the shelf’, with patients receiving the nearest match.

̽��ֱ��team is completing tests on the ideal combination of scaffold structure, peptide decoration and mix of cells to create a beating vascularised tissue. Next, the researchers will work with Dr Thomas Krieg in the Department of Medicine to graft the tissue into a rat heart. Their aim is to show that the patch makes vascular connections, integrates mechanically and electrically with heart muscle, and contracts in synchrony with the rest of the heart. Once they’ve accomplished this, they will scale up the size of the patches for future use in people.

“It’s exciting,” says Sinha. “We are recreating a tissue that has all the components we see in an organ, where the cells start talking together in mysterious and wonderful ways, and they start to work together as they do in the body. Our vision is that this technology will bring hope to the millions of patients worldwide who are suffering from heart failure, and allow them to lead a normal life again.”

It is almost impossible for an injured heart to fully mend itself. Within minutes of being deprived of oxygen – as happens during a heart attack when arteries to the heart are blocked – the heart’s muscle cells start to die. Sanjay Sinha wants to mend these hearts so that they work again.

We are recreating a tissue that has all the components we see in an organ, where the cells start talking together in mysterious and wonderful ways, and they start to work together as they do in the body.

Sanjay Sinha

̽��ֱ��District and Jonathan Settle

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Dish Life: a Cambridge Shorts film

amb206 — Mon, 21 Nov 2016 08:00:00 +0000

Stem cells are the stuff of life – but what’s it like to work with them in the lab? To unlock the secrets of how stem cells diversify into the different parts of our body, and pave the way to medical advances, scientists need to culture dishes of living material.

This isn’t as easy as it sounds: stem cells flourish only when they are happy. They need lots of food for a start. Because they excrete waste matter, the medium they live in needs replenishing. As they multiply, cells need splitting up so that they have enough space. Before long they’re hungry (and grubby) all over again.

Caring for stem cells, day in, day out, is a bit like looking after a gang of growing children. Dish Life employs a conversational style and enlists a group of real kids to explain some basic science. ̽��ֱ��scientists are the endlessly-patient parents and the cells the sometimes-unpredictable kids.

̽��ֱ��film opens a window on to the life of a scientist working with stem cells: life has to be organised around the demands of the cells. If stem cells are round and shiny, rather like Christmas tree decorations, they are healthy. If they are flat or spiky, they might be dying.

In an engaging and light-hearted way, Dish Life illustrates the high level of commitment required to work successfully with living cells in research that contributes to the development of new treatments for degenerative diseases. Being a scientist is fulfilling – but it’s also a lot of hard work.

Dish Life has won third place in the Raw Science Festival in Los Angeles.

Dish Life is one of four films made by Cambridge researchers for the 2016 Cambridge Shorts series, funded by Wellcome Trust ISSF. ̽��ֱ��scheme supports early career researchers to make professional quality short films with local artists and filmmakers. Researchers Dr Loriana Vitillo (Stem Cell Institute) and Karen Jent (Department of Sociology) collaborated with filmmaker Chloe Thomas.

Science is demanding as well as exciting. Dish Life, the final of four Cambridge Shorts films, compares the task of raising stem cells in the lab to the challenge of looking after a gang of unruly kids. In conversation with real-life children, scientists show how tricky it is to work with these ‘super cells’.

Dish Life

Still from Dish Life, a Cambridge Shorts film

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Scientists develop very early stage human stem cell lines for first time

cjb250 — Fri, 04 Mar 2016 08:41:37 +0000

As well as a potential source of stem cells for use in regenerative medicine, the technique could open up new avenues of research into disorders such as Down’s syndrome.

̽��ֱ��ability to derive naïve stem cells has been possible for over thirty years from mouse embryos, using a technique developed by Sir Martin Evans and Professor Matthew Kaufman during their time at Cambridge, but this is the first time this has been possible from human embryos.

Human pluripotent stem cells for use in regenerative medicine or biomedical research come from two sources: embryonic stem cells, derived from fertilised egg cells discarded from IVF procedures; and induced pluripotent stem cells, where skin cells are reprogrammed to a pluripotent form. However, these cells are already “primed” for differentiation into specific cell types. In contrast, all instructions have been erased in naïve cells, which may make it easier to direct them into any cell type of interest.

Recently naïve-like human induced pluripotent stem cells have been created by reprogramming but it has been unknown whether they can also be obtained directly from the human embryo.

When an egg cell is fertilised by a sperm, it begins to divide and replicate before the embryo takes shape. Around day five, the embryonic cells cluster together and form a structure called the ‘blastocyst’. This occurs before implantation into the uterus. ̽��ֱ��blastocyst comprises three cell types: cells that will develop into the placenta and allow the embryo to attach to the womb; and cells that form the ‘yolk sac’, which provides nutrients to the developing foetus; and the ‘epiblast’ comprising the naïve cells that will develop into the future body.

In research published today in the journal Stem Cell Reports, scientists from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute managed to remove cells from the blastocyst at around day six and grow them individually in culture. By separating the cells, the researchers in effect stopped them ‘talking’ to each other, preventing them from being steered down a particular path of development.

“Until now it hasn’t been possible to isolate these naïve stem cells, even though we’ve had the technology to do it in mice for thirty years – leading some people to doubt it would be possible,” explains Ge Guo, the study’s first author, “but we’ve managed to extract the cells and grow them individually in culture. Naïve stem cells have many potential applications, from regenerative medicine to modelling human disorders.”

Naïve pluripotent stem cells in principle have no restrictions on the types of adult tissue into which they can develop, which means they may have promising therapeutic uses in regenerative medicine to treat devastating conditions that affect various organs and tissues, particularly those that have poor regenerative capacity, such as the heart, brain and pancreas.

Dr Jenny Nichols, joint senior author of the study, says that one of the most exciting applications of their new technique would be to study disorders that arise from cells that contain an abnormal number of chromosomes. Ordinarily, the body contains 23 pairs of identical chromosomes (22 pairs and one pair of sex chromosomes), but some children are born with additional copies, which can cause problems – for example, children with Down’s syndrome are born with three copies of chromosome 21.

“Even in many ‘normal’ early-stage embryos, we find several cells with an abnormal number of chromosomes,” explains Dr Nichols. “Because we can separate the cells and culture them individually, we could potentially generate ‘healthy’ and ‘affected’ cell lines. This would allow us to generate and compare tissues of two models, one ‘healthy’ and one that is genetically-identical other than the surplus chromosome. This could provide new insights into conditions such as Down’s syndrome.”

̽��ֱ��research was supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Swiss National Science Foundation and the Wellcome Trust.

Reference
Guo, G et al. Naïve pluripotent stem cells derived directly from isolated cells of the human inner cell mass; Stem Cell Reports; e-pub 3 March 2015. DOI: 10.1016/j.stemcr.2016.02.005

Scientists at the ̽��ֱ�� of Cambridge have for the first time shown that it is possible to derive from a human embryo so-called ‘naïve’ pluripotent stem cells – one of the most flexible types of stem cell, which can develop into all human tissue other than the placenta.

Until now it hasn’t been possible to isolate human naïve stem cells, even though we’ve had the technology to do it in mice for thirty years – leading some people to doubt it would be possible

Ge Guo

Colonies of human naïve embryonic stem cells grown on mouse feeder cells

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Body builders: collagen scaffolds

lw355 — Wed, 04 Jun 2014 09:07:30 +0000

It may not look like much to the naked eye, but collagen is remarkably strong. ̽��ֱ��most abundant protein in the animal kingdom, it gives strength and structure to skin, tendons, ligaments, smooth muscle tissue and many other parts of the body.

Through precise manipulation at a structural level, collagen can also be used as a construction material in the laboratory or clinic to help regenerate new tissue, repair damaged cartilage and bone, or aid in the development of new therapies for cardiac disease, blood disorders and cancer.

To understand these conditions better and develop new treatments, or regenerate new tissue, researchers require models that very closely mimic the complex, three-dimensional environments found in human tissue.

As a natural material, collagen is ideal for these biomimetic applications. By shaping it into porous structures, collagen acts as a ‘scaffold’ on which cells and tissue can grow in three dimensions in predetermined forms, mimicking those found in the body.

̽��ֱ��idea of using collagen as a scaffold is not new, but the very high level of control that Cambridge researchers are able to achieve over its properties has made a huge range of clinical applications possible, including the repair of damaged joints or tissue, or accelerating the development of new therapies for cancer.

“There is an increasing need for improved materials that work with the systems in the body to regenerate healthy tissue, rather than just replacing what’s there with something synthetic,” said Professor Ruth Cameron of the Department of Materials Science and Metallurgy, who, along with Professor Serena Best, is working with researchers from across the ̽��ֱ�� to develop the scaffolds for a range of clinical applications. “You’re trying to help the body to heal itself and produce what it needs in order to do that.”

To build the scaffolds, the researchers begin with a solution of collagen and water and freeze it, creating ice crystals. As the collagen cannot incorporate into ice, it gathers around the edges of the crystals. When the pressure around the ice is dropped to very low levels, it converts directly from a solid to vapour, leaving the collagen structure behind. By precisely controlling how the ice crystals grow as the water freezes, the researchers are able to control the shape and properties of the resulting collagen scaffold.

By adding small groups of amino acids known as peptide sequences to the surface of the scaffold at different points, the way in which the collagen interacts with the growing cells changes, altering the potential uses for the scaffold. ̽��ֱ��peptide sequences signal certain cells to bind to the scaffold or to each other, while signalling other cells to migrate. Collectively, these signals direct the scaffold to form a certain type of tissue or have a certain type of biological response.

“ ̽��ֱ��scaffolds are a three-dimensional blank canvas – they can then be used in any number of different ways,” said Cameron, who is funded by the European Research Council. “They can be used to mimic the way in which natural tissue behaves, or they can be directed to form different sized or sequenced structures.”

̽��ֱ��technology has already gone from the laboratory all the way to patients, first as Chondromimetic, a product for the repair of damaged knee joints and bone defects associated with conditions such as osteoarthritis, trauma or surgery. By adding calcium and phosphate to the scaffold to mimic the structure of bone, it helps regenerate bone and cartilage. Chondromimetic has been through clinical trials and has received its CE mark, enabling its sale in Europe.

In future, the scaffolds could also see use as a treatment for cardiac disease. Working with Professor Richard Farndale from the Department of Biochemistry and Dr Sanjay Sinha from the Department of Medicine, and supported by funding from the British Heart Foundation, Best and Cameron are developing the scaffolds for use as patches to repair the heart after a heart attack.

Heart attacks occur when there is an interruption of blood to the heart, killing heart muscle. ̽��ֱ��remaining heart muscle then has to work harder to pump blood around the body, which can lead to a thickening of the heart wall and potential future heart failure.

By modifying the collagen scaffolds with the addition of peptide sequences, they could be used to grow new heart cells to ‘patch’ over areas of dead muscle, regenerating the heart and helping it function normally. Cells could be taken directly from the patient and reprogrammed to form heart cells through stem cell techniques.

While the work is still in its early stages, the scaffolds could one day be an important tool in treating coronary heart disease, which is the UK’s biggest killer. “These scaffolds give cells a foothold,” said Farndale, who is working with Sinha to characterise the scaffolds so that they encourage heart cells to grow. “Eventually, we hope to be able to use them, along with cells we’ve taken directly from the patient, to enable the heart to heal itself following cardiac failure.”

Another potentially important application for the scaffolds is in breast cancer research. By using them to grow mimics of breast tissue, the scaffolds could help accelerate the development of new therapies. Working with Professor Christine Watson in the Department of Pathology, Best and Cameron are fine-tuning the scaffolds so that they can be used to create three-dimensional models of breast tissue. If successful, this artificial breast tissue could assist with the screening of new drugs for breast cancer, reduce the number of animals used in cancer research and ultimately lead to personalised therapies.

“This is a unique culture system,” said Watson. “We are able to add different types of cells to the scaffold at different times, which no-one else can do. Better models will make our work as cancer researchers much easier, which will ultimately benefit patients.”

Like breast tissue, blood platelets also require a very specific environment to grow. Dr Cedric Ghevaert of the Department of Haematology is working with Best and Cameron to use the scaffold technology to create a bone-like niche to grow bone marrow cells, or megakaryocytes, for the production of blood platelets from adult stem cells. In theory, this could be used to produce platelets as and when they are needed, without having to rely on blood donations.

“ ̽��ֱ��technology for culturing the cells is actually quite generic, so the range of applications it could be used for in future is quite broad,” said Best. “In terms of clinical applications, it could be used in almost any situation where you’re trying to regenerate tissue.”

“In some senses, it can be used for anything,” added Cameron. “As you start to create highly organised structures made up of many different types of cells – such as the liver or pancreas – there is an ever-increasing complexity. But the potential of this technology is huge. It could make a huge difference for researchers and patients alike.”

Miniature scaffolds made from collagen – the ‘glue’ that holds our bodies together – are being used to heal damaged joints, and could be used to develop new cancer therapies or help repair the heart after a heart attack.

We are able to add different types of cells to the scaffold at different times, which no-one else can do

Christine Watson

Jennifer Ashworth

Collagen scaffold imaged using X-ray microtomography to reveal its 3D structure

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First randomised controlled trial to show spinal cord regeneration in dogs

fpjl2 — Mon, 19 Nov 2012 14:54:25 +0000

In a collaboration between the ̽��ֱ��’s Veterinary School and MRC’s Regenerative Medicine Centre, scientists used a unique type of cell to regenerate the damaged part of the dogs’ spines. ̽��ֱ��researchers are cautiously optimistic that the work could have a future role in the treatment of human patients with similar injuries if used alongside other treatments.

Scientists have been aware for over a decade that olfactory ensheathing cells (OEC) might be useful in treating the damaged spinal cord because of their unique properties. ̽��ֱ��cells have the ability to support nerve fibre growth that maintains a pathway between the nose and the brain.

Previous research using laboratory animals has already revealed that OECs can aid regeneration of the parts of nerve cells that transmit signals (axons) so as to form a ‘bridge’ between damaged and undamaged spinal cord tissue. A Phase 1 trial in human patients with SCI established that the procedure is safe.

̽��ֱ��study, published in the latest issue of the neurology journal Brain, is the first double-blinded randomised controlled trial to test the effectiveness of these transplants to improve function in ‘real-life’ spinal cord injury. ̽��ֱ��trial was performed on animals that had spontaneous and accidental injury rather than in the controlled environment of a laboratory, and some time after the injury occurred. This far more closely resembles the way in which the procedure might be used in human patients.

̽��ֱ��34 pet dogs had all suffered severe spinal cord injury. Twelve months or more after the injury, they were unable to use their back legs to walk and unable to feel pain in their hindquarters. Many of the dogs were dachshunds which are particularly prone to this type of injury. Dogs are also more likely to suffer from SCIs because the spinal cord may be damaged as a result of what in humans is the relatively minor condition of a slipped disc.

In the study, funded by the MRC, one group of dogs had olfactory ensheathing cells from the lining of their own nose injected into the injury site. ̽��ֱ��other group of dogs was injected with just the liquid in which the cells were transplanted. Neither the researchers nor the owners (nor the dogs!) knew which injection they were receiving.

̽��ֱ��dogs were observed for adverse reactions for 24 hours before being returned to their owners. From then on, they were tested at one month intervals for neurological function and to have their gait analysed on a treadmill while being supported in a harness. In particular, the researchers analysed the dogs’ ability to co-ordinate movement of their front and back limbs.

̽��ֱ��group of dogs that had received the OEC injection showed considerable improvement that was not seen in the other group. These animals moved previously paralysed hind limbs and co-ordinated the movement with their front legs. This means that in these dogs neuronal messages were being conducted across the previously damaged part of the spinal cord. However, the researchers established that the new nerve connections accounting for this recovery were occurring over short distances within the spinal cord and not over the longer distances required to connect the brain with the spinal cord.

Professor Robin Franklin, a co-author of the study from the Wellcome Trust-MRC Cambridge Stem Cell Institute, ̽��ֱ�� of Cambridge, said: “Our findings are extremely exciting because they show for the first time that transplanting these types of cell into a severely damaged spinal cord can bring about significant improvement. We’re confident that the technique might be able to restore at least a small amount of movement in human patients with spinal cord injuries but that’s a long way from saying they might be able to regain all lost function. It’s more likely that this procedure might one day be used as part of a combination of treatments, alongside drug and physical therapies, for example.”

Dr Rob Buckle, Head of Regenerative Medicine at the MRC, commented: “This proof of concept study on pet dogs with the type of injury sustained by human spinal patients is tremendously important and an excellent basis for further research in an area where options for treatment are extremely limited. It’s a great example of collaboration between veterinary and regenerative medicine researchers that has had an excellent outcome for the pet participants and potentially for human patients.”

̽��ֱ��researchers stress that human patients with a spinal injury rate a return in sexual function and continence far higher than improved mobility. Some of the dogs in the study did regain bowel and bladder control but the number of these was not statistically significant.

Mrs May Hay, owner of Jasper who took part in the trail (and can be seen in the video), said: “Before the trial, Jasper was unable to walk at all. When we took him out we used a sling for his back legs so that he could exercise the front ones. It was heartbreaking. But now we can’t stop him whizzing round the house and he can even keep up with the two other dogs we own. It’s utterly magic.”

Text courtesy of the Medical Research Council

Researchers have shown it is possible to restore co-ordinated limb movement in dogs with severe spinal cord injury (SCI).

Our findings are extremely exciting because they show for the first time that transplanting these types of cell into a severely damaged spinal cord can bring about significant improvement.

Robin Franklin

Cambridge Veterinary School

A dog called Jasper during the trial

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Teaching old cells new tricks

lw355 — Tue, 24 Apr 2012 14:41:44 +0000

How do you study a human disease that has no equivalent in animals and where the human cells in question are so hard to grow outside the body they cannot be tested in the laboratory? ̽��ֱ��answer, until now, was with great difficulty. But by using a new stem cell technique, that is set to change.

Dr Ludovic Vallier, who holds an MRC Senior Fellowship in the Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery at Cambridge in collaboration with Professor David Lomas (Cambridge Institute for Medical Research and Department of Medicine), works on a group of devastating genetic diseases affecting the liver.

“We target metabolic diseases of the liver, diseases such as alpha 1 antitrypsin deficiency. It’s one of the most common single genetic disorders and the protein it affects – which is only produced by the liver – is really important because it controls activity of elastase in the lung. Without this control, people develop serious lung problems and the disease also affects the liver, so these patients develop liver failure,” he explained.

̽��ֱ��problem is that these diseases cannot be studied in vitro – in a dish – in the laboratory, he said: “You can’t take cells from the liver of these very sick patients, and if you could they wouldn’t grow, which means you don’t have any way of screening drugs that could help treat these diseases.”

Without effective drugs, the only current treatment is a liver transplant. “There is a huge shortage of organs and transplantation involves taking immunosuppressive drugs, which is heavy treatment especially in already fragile patients,” Dr Vallier said. “And the disease is progressive so it’s very complicated to manage.” Understandably, Dr Vallier is excited that a new method of producing stem cells developed in Japan has given him and other researchers a way of studying these diseases and screening potential drugs to treat them.

“ ̽��ֱ��new technology consists of taking cells from skin and reprogramming them so that they become stem cells – cells that are capable of proliferating and differentiating into almost all tissue types,” he said.

This reprogramming means a cell with a previously fixed identity can be taught a new one – in this case taking skin cells and reprogramming them to become liver cells. When the skin cells come from a patient with liver disease, these skin-turned-liver cells also have the disease, making them ideal for studying the disease and screening potential drugs to treat it.

According to Dr Vallier: “Because we can generate liver cells that mimic the disease of the original patient in vitro, that allows us to do basic studies that were impossible by biopsy or primary culture and also to do drug screening.” And because the skin cells can come from a whole range of people, it gives researchers access to a broad diversity of patients as well as overcoming some of the ethical concerns associated with embryonic stem cells.

“That’s a very important step because it solves the problems associated with a limited stock of stem cells,” he said, “and because it’s a simple method, it’s easily accessible to a wide number of laboratories.”

Showing this can be done in a small number of liver patients in Cambridge is an important proof of concept, and supports the possibility that a similar approach might be applicable to a wide range of other serious diseases that still lack effective treatments, including neurodegenerative diseases such as Parkinson’s and Alzheimer’s Disease as well as heart diseases.

And Cambridge – which now has almost 30 groups doing stem cell research and strong links between academic researchers and clinicians – is perfectly positioned to make the most of this new technique.

“ ̽��ֱ��Laboratory for Regenerative Medicine is starting to become an expert in this disease modelling and we are all part of a larger consortium, the Cambridge Stem Cell Initiative (SCI),” said Dr Vallier. “Together, we are putting together resources and scientific interest to really develop stem cells and their clinical application. ̽��ֱ��SCI is a unique consortium because it brings together a wealth of complementary expertise.”

While this first revolution involves in vitro disease modelling and drug screening, Dr Vallier hopes this work will ultimately lead to personalised cell-based therapies where liver cells reprogrammed from a patient’s own skin cells could be used in place of a liver transplant. “It will take time for us to assess this clinical use and show that it is safe as well as effective,” he explained, “but if you ask me again in five years I should be able to tell you whether we are going to do it.”

Much hyped by the media, stem cells have tremendous power to improve human health. As part of the Cambridge Stem Cell Initiative, Dr Ludovic Vallier’s research in the Anne McLaren Laboratory for Regenerative Medicine shows how stem cells can further our understanding of disease and help deliver much-needed new treatments.

̽��ֱ��new technology consists of taking cells from skin and reprogramming them so that they become stem cells – cells that are capable of proliferating and differentiating into almost all tissue types.

Dr Ludovic Vallier

Candy Cho

Stem cells

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