̽��ֱ�� of Cambridge - Anne McLaren Laboratory for Regenerative Medicine

AstraZeneca/GSK/ ̽��ֱ�� of Cambridge collaborate to support UK national effort to boost COVID-19 testing

plc32 — Tue, 07 Apr 2020 10:46:52 +0000

A new testing laboratory will be set up by AstraZeneca, GSK and Cambridge at the ̽��ֱ��’s Anne McLaren Building. This facility will be used for high throughput screening for COVID-19 testing and to explore the use of alternative chemical reagents for test kits in order to help overcome current supply shortages.

Alongside this new testing facility, AstraZeneca and GSK are working together to provide process optimisation support to the UK national testing centres in Milton Keynes, Alderley Park and Glasgow for COVID-19, providing expertise in automation and robotics to help the national testing system to continue to expand capacity over the coming weeks.

While diagnostic testing is not part of either company’s core business, we are moving as fast as we can to help where possible - with a focus on providing our world class scientific and technical expertise - working both with the Government’s screening programme and alongside the wider life sciences sector and specialist diagnostic companies.

Further updates on progress will be issued on this work in due course.

We continue to pay tribute to those working on the frontlines of this pandemic, in the UK and globally. Defeating COVID-19 requires a collective effort from everyone working in healthcare and we are committed to playing our part.

As part of the UK Government’s announcement of a new five pillar plan to boost testing for COVID-19, AstraZeneca, GSK and the ̽��ֱ�� of Cambridge have formed a joint collaboration to take action to support this national effort.

Everyone in this ̽��ֱ�� and private industry partnership is working hard to help our health service fight COVID-19.

Vice-Chancellor Stephen J Toope

̽��ֱ��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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Stem cells likely to be safe for use in regenerative medicine, study confirms

cjb250 — Fri, 18 Dec 2015 10:59:29 +0000

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 ‘reset’ to their original, pluripotent form. They are seen as having 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.

However, some scientists have been concerned that the cells may not incorporate properly into the body and hence not proliferate or distribute themselves as intended, resulting in tumours. Today’s study suggests that this will not be the case and that stem cells, when transplanted appropriately, are likely to be safe for use in regenerative medicine.

Professor Roger Pedersen from the Anne McLaren Laboratory for Regenerative Medicine at the ̽��ֱ�� of Cambridge, commenting on co-author Victoria Mascetti’s research findings, says: “Our study provides strong evidence to suggest that human stem cells will develop in a normal – and importantly, safe – way. This could be the news that the field of regenerative medicine has been waiting for.”

̽��ֱ��best way to test how well stem cells would incorporate into the body is to transplant them into an early-stage embryo and see how they develop. As this cannot be done ethically in humans, scientists use mouse embryos. ̽��ֱ��gold standard test, developed in Cambridge in the 1980s, involves putting the stem cells into a mouse blastocyst, a very early stage embryo after fertilisation, then assessing stem cell contribution to the various tissues of the body.

Previous research has not succeeded in getting human pluripotent stem cells to incorporate into embryos. However, in research funded by the British Heart Foundation, Victoria Mascetti and Professor Pedersen have shown that it is possible to successfully transplant human pluripotent stem cells into the mouse embryo and that they then develop and grow normally.

Image: Mouse embryo with human pluripotent stem cells (red) incorporated into the brain region

“Stem cells hold great promise for treating serious conditions such as heart disease and Parkinson’s disease, but until now there has been a big question mark over how safe and effective they will be,” explains Professor Pedersen.

Mascetti’s research breakthrough in this new study was to demonstrate that human pluripotent stem cells are equivalent to an embryonic counterpart. Where attempts to incorporate human pluripotent stem cells had failed previously, it was because the stem cells had not been matched to the correct stage of embryo development: the cells needed to be transplanted into the mouse embryo at a later stage than was previously thought (a stage of embryo development known as gastrulation). Once transplanted at the correct stage, the stem cells went on to grow and proliferate normally, to integrate into the embryo and to distribute themselves correctly across relevant tissues.

Ms Mascetti adds: “Our finding that human stem cells integrate and develop normally in the mouse embryo will allow us to study aspects of human development during a window in time that would otherwise be inaccessible.”

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, which helped fund the study, said: “These results substantially strengthen the view that induced pluripotent stem cells from adult tissue are suitable for use in regenerative medicine – for example in attempts to repair damaged heart muscle after a heart attack.

“ ̽��ֱ��Cambridge team has shown definitively that when stem cells are introduced into early mouse embryos under the right conditions, they multiply and contribute in the correct way to all the cell types that are formed as the embryo develops.”

Reference
Victoria L Mascetti and Roger A Pedersen. Human-Mouse Chimerism Validates Human Stem Cell Pluripotency. Cell Stem Cell; 17 Dec 2015

Cambridge researchers have found the strongest evidence to date that human pluripotent stem cells – cells that can give rise to all tissues of the body – will develop normally once transplanted into an embryo. ̽��ֱ��findings, published today in the journal Cell Stem Cell, could have important implications for regenerative medicine.

Our study provides strong evidence to suggest that human stem cells will develop in a normal – and importantly, safe – way. This could be the news that the field of regenerative medicine has been waiting for

Roger Pedersen

Roger Pederson/Victoria Mascetti

Mouse embryo yolk sac with human pluripotent stem cells (green) incorporated

̽��ֱ��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 grow ‘mini-lungs’ to aid the study of cystic fibrosis

cjb250 — Fri, 20 Mar 2015 10:00:10 +0000

̽��ֱ��research is one of a number of studies that have used stem cells – the body’s master cells – to grow ‘organoids’, 3D clusters of cells that mimic the behaviour and function of specific organs within the body. Other recent examples have been ‘mini-brains’ to study Alzheimer’s disease and ‘mini-livers’ to model liver disease. Scientists use the technique to model how diseases occur and to screen for potential drugs; they are an alternative to the use of animals in research.

Cystic fibrosis is a monogenic condition – in other words, it is caused by a single genetic mutation in patients, though in some cases the mutation responsible may differ between patients. One of the main features of cystic fibrosis is the lungs become overwhelmed with thickened mucus causing difficulty breathing and increasing the incidence of respiratory infection. Although patients have a shorter than average lifespan, advances in treatment mean the outlook has improved significantly in recent years.

Researchers at the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute used skin cells from patients with the most common form of cystic fibrosis caused by a mutation in the CFTR gene referred to as the delta-F508 mutation. Approximately three in four cystic fibrosis patients in the UK have this particular mutation. They then reprogrammed the skin cells to an induced pluripotent state, the state at which the cells can develop into any type of cell within the body.

Using these cells – known as induced pluripotent stem cells, or iPS cells – the researchers were able to recreate embryonic lung development in the lab by activating a process known as gastrulation, in which the cells form distinct layers including the endoderm and then the foregut, from which the lung ‘grows’, and then pushed these cells further to develop into distal airway tissue. ̽��ֱ��distal airway is the part of the lung responsible for gas exchange and is often implicated in disease, such as cystic fibrosis, some forms of lung cancer and emphysema.

̽��ֱ��results of the study are published in the journal Stem Cells and Development.

“In a sense, what we’ve created are ‘mini-lungs’,” explains Dr Nick Hannan, who led the study. “While they only represent the distal part of lung tissue, they are grown from human cells and so can be more reliable than using traditional animal models, such as mice. We can use them to learn more about key aspects of serious diseases – in our case, cystic fibrosis.”

̽��ֱ��genetic mutation delta-F508 causes the CFTR protein found in distal airway tissue to misfold and malfunction, meaning it is not appropriately expressed on the surface of the cell, where its purpose is to facilitate the movement of chloride in and out of the cells. This in turn reduces the movement of water to the inside of the lung; as a consequence, the mucus becomes particular thick and prone to bacterial infection, which over time leads to scarring – the ‘fibrosis’ in the disease’s name.

Using a fluorescent dye that is sensitive to the presence of chloride, the researchers were able to see whether the ‘mini-lungs’ were functioning correctly. If they were, they would allow passage of the chloride and hence changes in fluorescence; malfunctioning cells from cystic fibrosis patients would not allow such passage and the fluorescence would not change. This technique allowed the researchers to show that the ‘mini-lungs’ could be used in principle to test potential new drugs: when a small molecule currently the subject of clinical trials was added to the cystic fibrosis ‘mini lungs’, the fluorescence changed – a sign that the cells were now functioning when compared to the same cells not treated with the small molecule.

“We’re confident this process could be scaled up to enable us to screen tens of thousands of compounds and develop mini-lungs with other diseases such as lung cancer and idiopathic pulmonary fibrosis,” adds Dr Hannan. “This is far more practical, should provide more reliable data and is also more ethical than using large numbers of mice for such research.”

̽��ֱ��research was primarily funded by the European Research Council, the National Institute for Health Research Cambridge Biomedical Research Centre and the Evelyn Trust.

Inset image: Branching mini-lung. Credit: Nick Hannan, ̽��ֱ�� of Cambridge

Reference
Hannan, NR et al. Generation of Distal Airway Epithelium from Multipotent Human Foregut Stem Cells. Stem Cells and Development; 10 March 2015.

Scientists at the ̽��ֱ�� of Cambridge have successfully created ‘mini-lungs’ using stem cells derived from skin cells of patients with cystic fibrosis, and have shown that these can be used to test potential new drugs for this debilitating lung disease.

We can use these 'mini-lungs' to learn more about key aspects of serious diseases – in our case, cystic fibrosis

Nick Hannan

Hey Paul Studios

Blue and Brown Anatomical Lung Wall Decor

̽��ֱ��text in this work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page. For image rights, please see the credits associated with each individual image.

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Attribution

Testing time for stem cells

lw355 — Thu, 23 Oct 2014 09:27:30 +0000

Much has been written about the promise of stem cells for modern medicine, and cell-based therapies to treat diseases are now being developed by commercial companies in Europe and across the world. But it is their use both to screen medicinal drugs for toxicity and to identify potential new therapies which is increasingly being viewed as one that could have an immediate and far-reaching impact.

Cambridge-based company DefiniGEN supplies the pharmaceutical industry with liver and pancreatic cells that have been reprogrammed from human skin cells. These cells, known as induced pluripotent stem (IPS) cells, are used to test potential new drugs, and can also be used as in vitro models for disease.

̽��ֱ��company spun out of the ̽��ֱ�� in 2012 and is one of the first commercial opportunities to arise from Cambridge’s expertise in stem cell research. Its portfolio of products is based on the research of Dr Ludovic Vallier, Professor Roger Pedersen, Dr Tamir Rashid, Dr Nick Hannan and Dr Candy Cho at the Anne McLaren Laboratory for Regenerative Medicine (LRM) in Cambridge.

“Drug failure in the late phase of clinical development is a major challenge to finding new therapeutics which are urgently needed by a broad number of patients with major health-care problems such as diabetes,” said Vallier. “A great deal of time and money are often lost following these false leads, and this limits the capacity of pharmaceutical companies to explore novel therapies. So, identifying toxic drugs as early as possible is vital to the efficiency and safety of the drug discovery process.

“Because we use human cells, our lab has a specific philosophy that all the data we generate is used not only for fundamental research, but also relates back to the clinic,” added Vallier, who holds a joint appointment at the LRM and the Wellcome Trust Sanger Institute, and is also Chief Scientific Officer at DefiniGEN. “We are interested in how stem cells work but we also always ask how the research we’re doing might have a clinical or translational interest.”

IPS cells can be grown outside the body indefinitely, but can also develop into almost any other cell type, providing the opportunity to have a ready source of human cells for testing new drugs. Vallier’s lab is combining basic knowledge in developmental biology and stem cells to develop methods for differentiating IPS cells into liver and pancreatic cells. Despite being generated in a dish, these cells show many of the same characteristics as those generated through natural development.

In particular, the group uses a mix of IPS cells and human embryonic stem (ES) cells to understand the molecular mechanisms that could govern the onset of various metabolic diseases such as those that affect the liver and pancreas.

̽��ֱ��liver is a large and complex organ and plays a number of important roles in the body, including digestion and the secretion and production of proteins. It is also the key organ for metabolising drugs and removing toxic substances from the body. For this reason, demonstrating that a drug candidate is not toxic to the liver is a crucial stage in the development of new drugs. It is also a test that most new drug candidates fail – increasing the cost and decreasing the efficiency of the drug development process.

A lack of high-quality human liver cells, or primary hepatocytes, means that inferior models are often used for testing potential new drugs. ̽��ֱ��cells generated in Vallier’s lab, however, show many of the same functional characteristics as primary hepatocytes, both for toxicology testing and as models of liver disease, including the most commonly inherited metabolic conditions such as familial hypercholesterolaemia and alpha 1-antitrypsin disorder.

Vallier’s team is also able to use these cells to model a diverse range of inherited liver diseases, offering the potential to accelerate the development of new therapies for these conditions. “There is no cure for end-stage liver disease apart from transplantation,” said Vallier. “Due to an acute shortage of donors, many research groups have been looking at alternative means of treating liver failure, including stem-cell-based therapy.”

Understanding the basic mechanisms behind the genesis and development of liver disease is helping his team develop new ways to generate functional liver cells that could be used to treat these conditions in future.

̽��ֱ��researchers are taking a similar approach to the pancreas, with a particular focus on diabetes. According to Diabetes UK, 3.2 million people in the UK have been diagnosed with diabetes, and an estimated 630,000 people have the condition, but don’t know it.

A promising therapy to treat type 1 diabetes is transplanting the insulin-producing islet cells of the pancreas, but there are only enough donated islets to treat fewer than 1% of diabetic patients who might benefit from this form of treatment.

Vallier’s group is working to generate large numbers of pancreatic islet cells from stem cells, which could be used for transplantation-based therapy. In addition, they are building in vitro models to study the molecular mechanisms that control pancreatic specification in the embryo. Vallier’s group has identified several genes that could be important for pancreatic development and in determining an individual’s resistance to diabetes.

“Using IPS cells, we’re trying to understand how individual genetics can influence development, insulin production capacity and disease onset,” said Vallier. “Essentially, human IPS cells can be used to model human genetics in a dish, which hasn’t been possible until now.

“Thanks to IPS cells, we’re now able to discover things that are not possible to do using animal models or any in vitro system. Not only will this help us understand more about the mechanisms behind human development, such as how cells in the human embryo develop into organs, but it will also help with drug screening and with making more-precise drugs, which is what’s really needed for the liver and pancreas. These types of in vitro applications are possible now, while cell-based treatments are more in the longer term. But you have to walk before you can run.”

DefiniGEN is one of the first commercial opportunities to arise from Cambridge’s expertise in stem cell research. Here, we look at some of the fundamental research that enables it to supply liver and pancreatic cells for drug screening.

Thanks to IPS cells, we’re now able to discover things that are not possible to do using animal models or any in vitro system

Ludovic Vallier

̽��ֱ��District

Testing time for stem cells

Yes

̽��ֱ��role of stem cells in developing new drugs

Anonymous — Tue, 30 Oct 2012 13:00:42 +0000

̽��ֱ��potential therapeutic applications of stem cells – such as regenerating damaged tissues or organs – have generated a great deal of interest over the past decade. While these types of applications are exciting, it is a long journey from lab to clinic. ̽��ֱ��most immediate impact of stem cells on human health will most likely come from their use in the development of new drugs.

̽��ֱ��ability to generate stem cells by reprogramming cells from patients’ skin has revolutionised human stem cell research. These cells, known as human induced pluripotent stem cells (hIPSC), can be differentiated into almost any cell type, allowing the opportunity to have a ready source of human cells for testing new therapies.

DefiniGEN, a new spin-out company from the ̽��ֱ�� of Cambridge, has been formed to supply hIPSC-derived cells to the drug discovery and regenerative medicine sectors. ̽��ֱ��company is based on the research of Dr Ludovic Vallier, Dr Tamir Rashid and Professor Roger Pedersen of the Anne McLaren Laboratory of Regenerative Medicine.

Dr Vallier led a team, including Dr Rashid, Dr Nick Hannan and Candy Cho, that developed the technology to generate human liver cells (hepatocytes) in a highly reproducible and scalable manner for commercial use. This represents a major breakthrough in the costly and time-consuming process of developing new therapies. ̽��ֱ��technology has also been used to effectively model a diverse range of inherited liver diseases and has the potential to accelerate the development of new therapies for these conditions.

̽��ֱ��liver is the key organ for metabolising drugs and removing toxins from the body. Consequently, it is often affected by toxic compounds. Demonstrating that a new drug candidate is free from liver toxicity is a key test in the development process, and it is a test that most drug candidates fail.

“If a drug’s failure occurs in the clinical phase of development, a great deal of time and money will have been lost,” said Dr Vallier. “Therefore, identifying toxic drugs as early as possible is vital to the safety and efficiency of the drug discovery process.”

Currently, either primary human hepatocytes or immortalised cell lines are used for toxicity testing. Primary hepatocytes have a high degree of batch-to-batch variation, are expensive and difficult to obtain in suitable quantities, while immortalised cell lines are an inferior model for toxicity testing.

̽��ֱ��hIPSC-derived cells produced by DefiniGEN, however, show many of the functional characteristics of primary cells, are highly reproducible and can be made in large quantities, making them ideal for toxicity testing.

In addition, the company’s OptiDIFF platform has produced libraries of disease-modelled cells for a range of diseases, including the most common inherited metabolic conditions such as Familial hypercholesterolemia and Alpha 1 anti-trypsin disorder. ̽��ֱ��cells effectively demonstrate key pathologies of diseases and can be used to improve lead optimisation studies, assisting the development of new therapies for these conditions.

̽��ֱ��company will also develop pancreatic beta cell products which, in combination with hepatocyte products, will enable the optimised development of new therapeutics for diabetes.

“This is a technology whose time has come,” said Dr Marcus Yeo, DefiniGEN’s CEO. “Cambridge has more expertise in the area of stem cells than perhaps anywhere else on earth, and now we are starting to see promising commercial opportunities which build on that expertise.”

DefiniGEN is based in Cambridge, and has been funded by a group led by Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm, along with members of Cambridge Angels and Cambridge Capital Group.

Cambridge team which developed method to generate liver cells from skin cells has formed a new company to supply stem cell products to the drug discovery and regenerative medicine sectors.

Cambridge has more expertise in the area of stem cells than perhaps anywhere else on earth, and now we are starting to see promising commercial opportunities which build on that expertise.

Dr Marcus Yeo

Ludovic Vallier

Differentiation of human Induced Pluripotent Stem Cells (hIPSC) to functional liver hepatocyte cells

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Yes

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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Yes