Study Reveals the Genetic Start-up of a Human Embryo

Study Reveals the Genetic Start-up of a Human Embryo

Thursday, 03 September 2015

An international team of scientists led from Sweden’s Karolinska Institutet has for the first time mapped all the genes that are activated in the first few days of a fertilised human egg. The study, which is being published in the journal Nature Communications, provides an in-depth understanding of early embryonic development in human – and scientists now hope that the results will help finding for example new therapies against infertility.

At the start of an individual’s life there is a single fertilised egg cell. One day after fertilisation there are two cells, after two days four, after three days eight and so on, until there are billions of cells at birth. The order in which our genes are activated after fertilisation has remained one of the last uncharted territories of human development.

Juha Kere is a Professor of Molecular Genetics at

Karolinska Institutet. Credit: Ulf Sirborn.

There are approximately 23,000 human genes in total. In the current study, scientists found that only 32 of these genes are switched on two days after fertilization, and by day three there are 129 activated genes. Seven of the genes found and characterised had not been discovered previously.

“These genes are the ‘ignition key’ that is needed to turn on human embryonic development. It is like dropping a stone into water and then watching the waves spread across the surface”, says principal investigator Juha Kere, professor at theDepartment of Biosciences and Nutrition at Karolinska Institutet and also affiliated to the SciLifeLab facility in Stockholm.

The researchers had to develop a new way of analysing the results in order to find the new genes. Most genes code for proteins but there are a number of repeated DNA sequences that are often considered to be so-called ‘junk DNA’, but are in fact important in regulating gene expression.

Treatment of infertility

In the current study, the researchers show that the newly identified genes can interact with the ‘junk DNA’, and that this is essential to the start of development.

Outi Hovatta is a Professor of Obstetrics and

Gynaecology at Karolinska Institutet. Credit:

Ulf Sirborn.

“Our results provide novel insights into the regulation of early embryonic development in human. We identified novel factors that might be used in reprogramming cells into so-called pluripotent stem cells for possible treatment of a range of diseases, and potentially also in the treatment of infertility”, says Outi Hovatta, professor at Karolinska Institutet’s Department of Clinical Science, Intervention and Technology, and a senior author.

The study was a collaboration between three research groups from Sweden and Switzerland that each provided a unique set of skills and expertise. The work was supported by the Karolinska Institutet Distinguished Professor Award, the Swedish Research Council, the Strategic Research Program for Diabetes funding at Karolinska Institutet, Stockholm County, the Jane & Aatos Erkko Foundation, the Instrumentarium Science Foundation, and the Åke Wiberg and Magnus Bergvall foundations. The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX).

Source: Karolinska Institutet

Contact: KI Press Office

Reference:

Novel PRD-like homeodomain transcription factors and retrotransposon elements in early human development

Virpi Töhönen, Shintaro Katayama, Liselotte Vesterlund, Eeva-Mari Jouhilahti, Mona Sheikhi, Elo Madissoon, Giuditta Filippini-Cattaneo, Marisa Jaconi, Anna Johnsson, Thomas R. Bürglin, Sten Linnarsson, Outi Hovatta and Juha Kere

Nature Communications, 3 September 2015, doi: 10.1038/NCOMMS9207

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Recovery of Sensory Function by Stem Cell Transplants

Recovery of Sensory Function by Stem Cell Transplants

Monday, 08 June 2015

New research from Uppsala University shows promising progress in the use of stem cells for treatment of spinal cord injury. The results, which are published in the scientific journal Scientific Reports, show that human stem cells that are transplanted to the injured spinal cord contribute to restoration of some sensory functions.

Traffic accidents and severe falls can cause ruptures of nerve fibres that enter/exit the spinal cord. Most commonly, these avulsion injuries affect the innervation of the arm and hand, and lead to paralysis, loss of sensation and cause chronic pain. Surgical interventions can help the patient regain some muscle function, but there is currently no treatment able to restore sensory functions. The reason for this is the emergence of a "barrier" at the junction between the ruptured nerve fibres and the spinal cord which prevents them from growing into the spinal cord and restore lost nerve connections.

In a new study the PhD students Jan Hoeber, Niclas König and Carl Trolle, working in Dr.Elena Kozlova's research group transplanted human stem cells to an avulsion injury in mice with the aim to restore a functional route for sensory information from peripheral tissues into the spinal cord.

The results show that the transplanted stem cells act as a "bridge" which allows injured sensory nerve fibres to grow into the spinal cord, rebuilds functional nerve connections, and thereby achieve long term restoration of major parts of the lost sensory functions. The transplanted stem cells differentiated to different types of cells with variable level of maturation, specific for the nervous system. No signs of tumour development or any functional abnormalities from the transplants were observed in the study, outcomes which are important in view of potential risks with transplantation of embryonic stem cells.

The results encourage further research on the use of stem cells for treatment of injury and disease in the spinal cord, and may contribute to the development of novel treatment strategies in these disorders.

Source: Uppsala University

Contact: Elena Kozlova

Reference:

Human embryonic stem cell-derived progenitors assist functional sensory regeneration after dorsal root avulsion injury

Hoeber J, Trolle C, König N, Du Z, Gallo A, Hermans E, Aldskogius H, Shortland P, Zheng, S-C, Deumens R, Kozlova EN. 

Scientific Reports 5, 08 June 2015, Article number: 10666, doi:10.1038/srep10666

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Do Viruses Make Us Smarter?

Do Viruses Make Us Smarter?

Monday, 12 January 2015

A new study from Lund University in Sweden indicates that inherited viruses that are millions of years old play an important role in building up the complex networks that characterise the human brain.

Researchers have long been aware that endogenous retroviruses constitute around five per cent of our DNA. For many years, they were considered junk DNA of no real use, a side-effect of our evolutionary journey.

In the current study, Johan Jakobsson and his colleagues show that retroviruses seem to play a central role in the basic functions of the brain, more specifically in the regulation of which genes are to be expressed, and when. The findings indicate that, over the course of evolution, the viruses took an increasingly firm hold on the steering wheel in our cellular machinery. The reason the viruses are activated specifically in the brain is probably due to the fact that tumours cannot form in nerve cells, unlike in other tissues.

"We have been able to observe that these viruses are activated specifically in the brain cells and have an important regulatory role. We believe that the role of retroviruses can contribute to explaining why brain cells in particular are so dynamic and multifaceted in their function. It may also be the case that the viruses' more or less complex functions in various species can help us to understand why we are so different", says Johan Jakobsson, head of the research team for molecular neurogenetics at Lund University.

The article, based on studies of neural stem cells, shows that these cells use a particular molecular mechanism to control the activation processes of the retroviruses. The findings provide us with a complex insight into the innermost workings of the most basal functions of the nerve cells. At the same time, the results open up potential for new research paths concerning brain diseases linked to genetic factors.

"I believe that this can lead to new, exciting studies on the diseases of the brain. Currently, when we look for genetic factors linked to various diseases, we usually look for the genes we are familiar with, which make up a mere two per cent of the genome. Now we are opening up the possibility of looking at a much larger part of the genetic material which was previously considered unimportant. The image of the brain becomes more complex, but the area in which to search for errors linked to diseases with a genetic component, such as neurodegenerative diseases, psychiatric illness and brain tumours, also increases".

Source: Lund University

Contact: Johan Jakobsson

Reference:

TRIM28 represses transcription of endogenous retroviruses in neural progenitor cells

Liana Fasching, Adamandia Kapopoulou, Rohit Sachdeva, Rebecca Petri, Marie E. Jönsson, Christian Männe, Priscilla Turelli, Patric Jern, Florence Cammas, Didier Trono, Johan Jakobsson

Cell Reports, 2015 Jan 6;10(1):20-8, doi: 10.1016/j.celrep.2014.12.004

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World's first child born after uterus transplantation

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Migrating Stem Cells Possible New Focus for Stroke Treatment

Migrating Stem Cells Possible New Focus for Stroke Treatment

Tuesday, 27 May 2014

Brain pericyte. Credit: Lund University.

Two years ago, a new type of stem cell was discovered in the brain that has the capacity to form new cells. The same research group at Lund University in Sweden has now revealed that these stem cells, which are located in the outer blood vessel wall, appear to be involved in the brain reaction following a stroke.

The findings show that the cells, known as pericytes, drop out from the blood vessel, proliferate and migrate to the damaged brain area where they are converted into microglia cells, the brain's inflammatory cells.

Pericytes are known to contribute to tissue repair in a number of organs, and the researchers believe that their reparative properties could also apply to the brain. The study shows for the first time that pericytes are directly involved in the reaction of the brain tissue after stroke.

"Pericytes are a fascinating cell type with many different properties and found at high density in the brain. It was surprising that a pericyte subtype is so strongly activated after a stroke. The fact that pericytes can be converted into microglia, which have an important function in the brain after a stroke, was an unexpected finding that opens up a new possibility to influence inflammation associated with a stroke", said Gesine Paul-Visse, neurologist at Lund University and senior author of the study.

Using a green fluorescent protein bound to the pericytes, the researchers were able to track the cells' path to the damaged part of the brain. The migration takes place within a week after a stroke. When the cells reach the site of damage they are converted into microglia cells, the 'cleaners' of the central nervous system. Inflammation can, however, have both positive reparative effects and negative effects on the damaged tissue. The exact role of microglia cells in the regeneration after a stroke is not entirely clear, but we do know that pericytes play an important role in protecting the brain against disease and injury.

"We now need to elucidate how pericytes affect the brain's recovery following a stroke. Our findings put pericytes in focus as a new target for brain repair and future research will help us understand more about the brain's own defence and repair mechanisms."

There is an urgent need for new drugs that can alleviate the harmful effects of a stroke as current treatment possibilities using thrombolysis are limited to the first hours following a stroke.

"Because inflammation following a stroke is an event that continues after the acute stage, we hope that targeting pericytes in the sub-acute phase after stroke, i.e. within a longer time window following the onset of stroke, may influence the outcome", said Gesine Paul-Visse.

Source: Lund University 

Contact: Gesine Paul-Visse

Reference:

Brain pericytes acquire a microglial phenotype after stroke
Ilknur Özen, Tomas Deierborg, Kenichi Miharada, Thomas PAdel, Elisabet Englund, Guillem Genove and Gesine Paul 

Acta Neuropathologica. May 2014, 10.1007/s00401-014-1295-x

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New Method Increases Supply of Embryonic Stem Cells

New Method Increases Supply of Embryonic Stem Cells

Monday, 27 January 2014

Single cell removal from an embryo.

A new method allows for large-scale generation of human embryonic stem cells of high clinical quality. It also allows for production of such cells without destroying any human embryos. The discovery is a big step forward for stem cell research and for the high hopes for replacing damaged cells and thereby curing serious illnesses such as diabetes and Parkinson's disease.

Currently human embryonic stem cells are made from surplus in vitro fertilized (IVF) embryos that are not used for the generation of pregnancies. The embryos do not survive the procedure. Therefore it has been illegal in the USA to use this method for deriving embryonic stem cell lines. Sweden's legislation has been more permissive. It has been possible to generate embryonic stem cells from excess, early IVF embryos with the permission of the persons donating their eggs and sperm.

Prof. Karl Tryggvason, KI.

An international research team led by Karl Tryggvason, Professor of Medical Chemistry at Karolinska Institute in Sweden and Professor at Duke-NUS Graduate Medical School in Singapore has, together with Professor Outi Hovatta at Karolinska Institute, developed a method that makes it possible to use a single cell from an embryo of eight cells. This embryo can then be re-frozen and, theoretically, be placed in a woman's uterus. The method is already used in Pre-implantation Genetic Diagnosis (PGD) analyses, where a genetic test is carried out on a single cell of an IVF embryo in order to detect potential hereditary diseases. If mutations are not detected, the embryo is inserted in the woman's uterus, where it can grow into a healthy child.

"We know that an embryo can survive the removal of a single cell. This makes a great ethical difference," says Karl Tryggvason.

The single stem cell is then cultivated on a bed of a human laminin protein known as LN-521 that is normally associated with pluripotent stem cells in the embryo. This allows the stem cell to duplicate and multiply without being contaminated. Previously the cultivation of stem cells has been done on proteins from animals or on human cells, which have contaminated the stem cells through uninhibited production of thousands of proteins.

"We can cultivate the stem cells in a chemically defined, clinical quality environment. This means that one can produce stem cells on a large scale, with the precision required for pharmaceutical production," says Karl Tryggvason.

Embryonic stem cells are pluripotent and can develop into any kind of cell. This means that they can become dopamine producing cells, insulin producing cells, heart muscle cells or eye cells, to name but a few of the hopes placed on cell therapy using stem cells.

"Using this technology the supply of human embryonic stem cells is no longer a problem. It will be possible to establish a bank where stem cells can be matched by tissue type, which is important for avoiding transplants being rejected," says Karl Tryggvason.

Source: Karolinska Institute

Contact: Press Office

Reference:

Clonal culturing of human embryonic stem cells on laminin-521/E-cadherin matrix in defined and xeno-free environment

Sergey Rodin, Liselotte Antonsson, Colin Niaudet, Oscar E. Simonson, Elina Salmela, Emil M. Hansson, Anna Domogatskaya, Zhijie Xiao, Pauliina Damdimopoulou, Mona Sheikhi, José Inzunza, Ann-Sofie Nilsson, Duncan Baker, Raoul Kuiper, Yi Sun, Elisabeth Blennow, Magnus Nordenskjöld, Karl-Henrik Grinnemo, Juha Kere, Christer Betsholtz, Outi Hovatta and Karl Tryggvason. 

Nature Communications, January 27, 2014, doi: 10.1038/ncomms4195

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Synthetic mRNA Can Induce Self-repair and Regeneration of the Infarcted Heart

Synthetic mRNA Can Induce Self-repair and Regeneration of the Infarcted Heart

Sunday, 08 September 2013

A team of scientists at Karolinska Institute and Harvard University has taken a major step towards treatment for heart attack, by instructing the injured heart in mice to heal by expressing a factor that triggers cardiovascular regeneration driven by native heart stem cells. The study, published in Nature Biotechnology, also shows that there was an effect on driving the formation of a small number of new cardiac muscle cells.

Dr. Kenneth Chien was recently recruited as a

researcher to Karolinska Institutet and now

share his time between Sweden and the US.

Credit: Ulf Sirborn. 

"This is the beginning of using the heart as a factory to produce growth factors for specific families of cardiovascular stem cells, and suggests that it may be possible to generate new heart parts without delivering any new cells to the heart itself ", says Kenneth Chien, a Professor at the medical university Karolinska Institute in Sweden and Harvard University, US, who led the research team behind the new findings.

The study is based upon another recent discovery in the Chien lab, which was published in Cell Research. This study shows that VEGFA, a known growth factor for vascular endothelial cells in the adult heart, can also serve as a switch that converts heart stem cells away from becoming cardiac muscle and towards the formation of the coronary vessels in the fetal heart. To coax the heart to make the VEGFA, the investigators in the Nature Biotechnology study used new technology where synthetic messenger RNA (mRNA) that encodes VEGFA is injected into the muscle cell. Then, heart muscle produces a short pulse of VEGFA. The mRNA is synthetically modified so that it escapes the normal defense system of the body that is known to reject and degrade the non-modified mRNA as a viral invader.

The study, performed in mice, shows that only a single administration of a short pulse of expression of VEGFA is required, if it can be delivered to the exact region where the heart progenitors reside. The therapeutic effect is long term, as shown by markedly improved survival following myocardial infarction with a single administration of the synthetic mRNA when given within 48 hours after the heart attack. The long-term effect appears to be based on changing the fate of the native heart stem cells from contributing to cardiac fibrotic scar tissue and towards cardiovascular tissue.

"This moves us very close to clinical studies to regenerate cardiovascular tissue with a single chemical agent without the need for injecting any additional cells into the heart," says Professor Chien.

At the same time, he points out that these are still early days and there remains much to be done. In particular, it will become of interest to engineer new device technology to deliver the synthetic mRNA via conventional catheter technology. It also will be critical to move these studies, which are based in mouse models, to other animals, which is currently in progress.

Source: Karolinska Institute

Contact: Katarina Sternudd

Reference:

Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction

Lior Zangi, Kathy O Lui, Alexander von Gise, Qing Ma, Wataru Ebina, Leon M Ptaszek, Daniela Später, Huansheng Xu, Mohammadsharif Tabebordbar, Rostic Gorbatov, Brena Sena, Matthias Nahrendorf, David M Briscoe, Ronald A Li, Amy J Wagers, Derrick J Rossi, William T Pu & Kenneth R Chien

Nature Biotechnology, 8 September 2013, DOI: 10.1038/nbt.2682

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Tumour Suppressor is needed for Stem Cells to Mature into Neurons

Tumour Suppressor is needed for Stem Cells to Mature into Neurons

Monday, 12 August 2013

CHD5 has previously been proposed as a tumour suppressor, acting as a brake that prevents healthy cells from developing into cancer cells. But the part played by the protein in healthy tissue, and whether this role is important for its ability to counter tumour growth, has remained largely uncharted. Working with colleagues at Trinity College in Dublin and BRIC in Copenhagen, researchers at Karolinska Institute have revealed its function in normal nervous system development and as a tumour suppressor.

The recently published study shows that when stem cells approach the final phase of their specialisation as neurons, CHD5 begins to be expressed at high levels. CHD5 can reshape the chromatin, in which DNA is packed around proteins, and in so doing either facilitate or obstruct the expression of genes. Ulrika Nyman, postdoc researcher in Dr Johan Holmberg's research group and one of the main authors of the current study, explains that on switching off CHD5 in the stem cells of mice embryos during the period in which the brain develops and the majority of neurons are formed, they found was that without CHD5, a stem cell is unable to silence the expression of a number of stem cell genes and genes that are actually to be expressed in muscle, blood or intestinal cells. They also observed an inability in the stem cell to switch on the expression of genes necessary for it to mature into a neuron, leaving it trapped in a stage between stem cell and neuron.

The gene that codes for CHD5 is found on part of chromosome 1 (1p36), which is often lost in tumour cells in a number of cancers, particularly neuroblastoma, a disease that strikes almost only children and which is thought to arise during the development of the peripheral nervous system. Neuroblastoma lacking this section of chromosome and thus also CHD5 are often more aggressive and more rapidly fatal. Treatment with retinoic acid can make immature nerve cells and some neuroblastoma cells mature into specialised nerve cells, but when the researchers prevented neuroblastoma cells from up-regulating CHD5, the tumours no longer responded to retinoic acid treatment.

"In the absence of CHD5, neural tumour cells cannot mature into harmless neurons, but continue to divide, making the tumour more malignant and much harder to treat," says Dr Holmberg at the Department of Cell and Molecular Biology.

"We now hope to be able to restore the ability to up-regulate CHD5 in aggressive tumour cells and make them mature into harmless nerve cells."

Source: Karolinska Institutet 

Contact: Johan Holmberg

Reference:

CHD5 Is Required for Neurogenesis and Has a Dual Role in Facilitating Gene Expression and Polycomb Gene Repression

Chris M. Egan, Ulrika Nyman, Julie Skotte, Gundula Streubel, Siobhán Turner, David J. O’Connell, Vilma Rraklli, Michael J. Dolan, Naomi Chadderton, Klaus Hansen, Gwyneth Jane Farrar, Kristian Helin, Johan Holmberg, Adrian P. Bracken

Developmental Cell, Volume 26, Issue 3, 223-236, 12 August 2013 10.1016/j.devcel.2013.07.008

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Stem Cell-based Bioartificial Tissues and Organs

Pioneering stem cell-based transplant technology is being developed and tested on new organs and tissues

Monday, 18 February 2013

Professor Paolo Macchiarini. 

Surgeon Paolo Macchiarini has made his name by successfully transplanting bioengineered stem cell-based trachea, composed of both artificial and biological material. He now plans to use the technique to recreate more complex tissues, such as the oesophagus and diaphragm or organs such as the heart and lungs. He has also made an experimental attempt to regenerate brain in mice and rats. This is part of the news he will be presenting during his seminar at the scientific AAAS Annual Meeting in Boston.

In June 2011, media all over the world reported about a ground breaking transplant, where a patient received an artificial trachea covered in his own stem cells. The result was an artificial windpipe with biological functions. To date, five operations have been carried out using this technique.

"We learn something from each operation. This means we can develop and refine the technique. We are also evaluating how we can transfer our experiences to other fields, such as neurology. The aim is to make as much use of the body's own healing potential as we can", says Paolo Macchiarini, Professor of Regenerative Surgery at Karolinska Institutet, and responsible for the surgery.

At the AAAS Annual Meeting, he will talk about how he believes the technology can be used in the future. This will include:

1.  The plan to operate on a 2 year-old girl in the USA in March. The girl was born without a trachea and has lived her entire life in intensive care, where she breathes through a tube placed in the oesophagus and connected directly to the lungs. Without a new trachea, she will never be able to leave the hospital. This will be the first time the procedure is conducted on a small child. It is also the first time the procedure will be conducted on an individual without a trachea - as previously, diseased organs have been replaced. 
2. There are also plans to transplant the oesophagus, an organ that is more complex than a trachea as it has muscles. 
3. In experimental trials on rats, the research team has investigated the possibility to replace brain matter that has been damaged by serious trauma sustained from events such as traffic accidents, gunshot wounds or surgery. The aim is to replace the lost brain matter with a cultivated stem cell based substance and in turn, avoid neurological damage. The experimental attempt that has been conducted on rats and mice has shown positive results. 
4.  On two occasions, severely injured patients with acute refractory lung failure received stem cell based therapy showing immediate functional improvement. Although both patients died as a consequence of multi-organ failure, the result has provided the first evidence that stem cell therapy can be a promising alternative to restore function in certain damaged organs - without the need for them to be removed and replaced with healthy donor organs.

Source: Karolinska Institutet 

Contact: Sabina Bossi

Reference:

Stem Cell-Based Bioartificial Tissues and Organs
Monday 18 February 09:45 am - 11:15 am
Hynes Convention Center, Boston, room 207

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New Stem Cell Found in the Brain

Finding could be key to developing methods to heal and repair brain injury and disease 
Friday, 20 April 2012

Researchers at Lund University in Sweden have discovered a new stem cell in the adult brain. These cells can proliferate and form several different cell types - most importantly, they can form new brain cells. Scientists hope to take advantage of the finding to develop methods to heal and repair disease and injury in the brain.

Analyzing brain tissue from biopsies, the researchers for the first time found stem cells located around small blood vessels in the brain. The cell's specific function is still unclear, but its plastic properties suggest great potential.

"A similar cell type has been identified in several other organs where it can promote regeneration of muscle, bone, cartilage and adipose tissue," said Patrik Brundin, M.D., Ph.D., Jay Van Andel Endowed Chair in Parkinson's Research at Van Andel Research Institute (VARI), Head of the Neuronal Survival Unit at Lund University and senior author of the study.

In other organs, researchers have shown clear evidence that these types of cells contribute to repair and wound healing. Scientists suggest that the curative properties may also apply to the brain. The next step is to try to control and enhance stem cell self-healing properties with the aim of carrying out targeted therapies to a specific area of the brain.

"Our findings show that the cell capacity is much larger than we originally thought, and that these cells are very versatile," said Gesine Paul-Visse, Ph.D., Associate Professor of Neuroscience at Lund University and the study's primary author.

"Most interesting is their ability to form neuronal cells, but they can also be developed for other cell types. The results contribute to better understanding of how brain cell plasticity works and opens up new opportunities to exploit these very features."

The study, published in the journal PLoS ONE, is of interest to a broad spectrum of brain research. Future possible therapeutic targets range from neurodegenerative diseases to stroke.

"We hope that our findings may lead to a new and better understanding of the brain's own repair mechanisms," said Dr. Paul-Visse.

"Ultimately the goal is to strengthen these mechanisms and develop new treatments that can repair the diseased brain."

About the Neuronal Survival Unit, Faculty of Medicine, Lund University

The research at Neuronal Survival Unit, Lund University, Sweden is focused on pathogenetic mechanisms and pharmacological treatment in cell and animal models of Parkinson's and Alzheimer's diseases. We also study cell replacement therapy with stem cells in attempts to repair brains in animal models of Parkinson's diseases. The group's mission is to understand neurodegenerative diseases and develop new therapies that are of benefit to patients and their caregivers.

About Van Andel Research Institute

Established by Jay and Betty Van Andel in 1996, Van Andel Institute is an independent research organization dedicated to preserving, enhancing and expanding the frontiers of medical science, and to achieving excellence in education by probing fundamental issues of education and the learning process. This is accomplished through the work of over 200 researchers in more than 20 on-site laboratories and in collaborative partnerships that span the globe.

Source: Van Andel Research Institute

Contact: Tim Hawkins

Reference:

The Adult Human Brain Harbors Multipotent Perivascular Mesenchymal Stem Cells
Gesine Paul, Ilknur Özen, Nicolaj S. Christophersen, Thomas Reinbothe, Johan Bengzon, Edward Visse, Katarina Jansson, Karin Dannaeus, Catarina Henriques-Oliveira, Laurent Roybon, Sergey V. Anisimov, Erik Renström, Mikael Svensson, Anders Haegerstrand, Patrik Brundin
PLoS ONE 7(4): e35577. doi:10.1371/journal.pone.0035577
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Stem Cells Can Repair a Damaged Cornea

Stem Cells Can Repair a Damaged Cornea  
Tuesday, 06 March 2012

This is Charles Hanson. Credit:

University of Gothenburg.

A new cornea may be the only way to prevent a patient going blind – but there is a shortage of donated corneas and the queue for transplantation is long. Scientists at the Sahlgrenska Academy at the University of Gothenburg, Sweden, have for the first time successfully cultivated stem cells on human corneas, which may in the long term remove the need for donators.

Approximately 500 corneal transplantations are carried out each year in Sweden, and about 100,000 in the world. The damaged and cloudy cornea that is turning the patient blind is replaced with a healthy, transparent one. But the procedure requires a donated cornea, and there is a severe shortage of donated material. This is particularly the case throughout the world, where religious or political views often hinder the use of donated material.

Replacing donated corneas

Scientists at the Sahlgrenska Academy, University of Gothenburg, have taken the first step towards replacing donated corneas with corneas cultivated from stem cells. Scientists Charles Hanson and Ulf Stenevi have used defective corneas obtained from the ophthalmology clinic at Sahlgrenska University Hospital in Mölndal. Their study is now published in the journal Acta Ophthalmologica, and shows how human stem cells can be caused to develop into what are known as "epithelial cells" after 16 days' culture in the laboratory and a further 6 days' culture on a cornea. It is the epithelial cells that maintain the transparency of the cornea.

First time ever on human corneas

"Similar experiments have been carried out on animals, but this is the first time that stem cells have been grown on damaged human corneas. It means that we have taken the first step towards being able to use stem cells to treat damaged corneas", says Charles Hanson.

"If we can establish a routine method for this, the availability of material for patients who need a new cornea will be essentially unlimited. Both the surgical procedures and the aftercare will also become much more simple", says Ulf Stenevi.

Few clinics conduct transplants

Only a few clinics are currently able to transplant corneas. Many of the transplantations in Sweden are carried out at the ophthalmology clinic at Sahlgrenska University Hospital, Department of Ophthalmology, Mölndal.

Source: University of Gothenburg

Contact: Charles Hanson

Reference:

Transplantation of human embryonic stem cells onto a partially wounded human cornea in vitro
Charles Hanson, Thorir Hardarson, Catharina Ellerström, Markus Nordberg, Gunilla Caisander, Mahendra Rao, Johan Hyllner, Ulf Stenevi
Acta Ophthalmologica on 27 January, DOI: 10.1111/j.1755-3768.2011.02358.x
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Unexpected Cell Repairs the Injured Spinal Cord

Unexpected Cell Repairs the Injured Spinal Cord
Friday, 08 July 2011
 
Lesions to the brain or spinal cord rarely heal fully, which leads to permanent functional impairment. After injury to the central nervous system (CNS), neurons are lost and largely replaced by a scar often referred to as the glial scar based on its abundance of supporting glial cells. Although this process has been known to science for over a century, the function of the scar tissue has long been disputed. However, there are indications that it stabilizes the tissue and that it inhibits the re-growth of damaged nerve fibres.

In this present study, Professor Jonas Frisén and his team of researchers show that the majority of scar cells in the damaged spinal cord are not glial cells at all, but derive from pericytes, a small group of cells located along blood vessels. They reveal that these pericytes start to divide after an injury, giving rise to a mass of connective tissue cells that migrate towards the lesion to form a large portion of the scar tissue. Their paper also shows that these cells are needed to regain the tissue integrity, and that in the absence of this reaction, holes appear in the tissue instead of scarring.

For many years, scientists have tried to modulate scar formation after CNS damage in order to facilitate functional recovery, and have concentrated on glial cells. However, these new findings indicate a critical and previously unknown mechanism for scar formation following damage to the nerve system, and give reason for further investigation into whether the modulation of pericytes after CNS injury can stimulate functional recovery.

Source: Karolinska Institutet
Contact: Ulla Bredberg

Reference:
A pericyte origin of spinal cord scar tissue
C. Göritz, D. Dias, N. Tomilin, M. Barbacid, O. Shupliakov, J. Frisén
Science online 8 July 2011 Vol. 333 no. 6039 pp. 238-242, DOI: 10.1126/science.1203165
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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/

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New Genetic Technique Converts Skin Cells into Brain Cells

New Genetic Technique Converts Skin Cells into Brain Cells
Friday, 10 June 2011

A research breakthrough has proven that it is possible to reprogram mature cells from human skin directly into brain cells, without passing through the stem cell stage. The unexpectedly simple technique involves activating three genes in the skin cells, genes that are already known to be active in the formation of brain cells at the foetal stage.

The new technique avoids many of the ethical dilemmas that stem cell research has faced.

For the first time, a research group at Lund University in Sweden has succeeded in creating specific types of nerve cells from human skin. By reprogramming connective tissue cells, called fibroblasts, directly into nerve cells, a new field has been opened up with the potential to take research on cell transplants to the next level. The discovery represents a fundamental change in the view of the function and capacity of mature cells. By taking mature cells as their starting point instead of stem cells, the Lund researchers also avoid the ethical issues linked to research on embryonic stem cells.

Head of the research group Malin Parmar was surprised at how receptive the fibroblasts were to new instructions.

“We didn’t really believe this would work, to begin with it was mostly just an interesting experiment to try. However, we soon saw that the cells were surprisingly receptive to instructions.”

The study, which was published in the latest issue of the scientific journal PNAS, also shows that the skin cells can be directed to become certain types of nerve cells.

In experiments where a further two genes were activated, the researchers have been able to produce dopamine brain cells, the type of cell which dies in Parkinson’s disease. The research findings are therefore an important step towards the goal of producing nerve cells for transplant, which originate from the patients themselves. The cells could also be used as disease models in research on various neurodegenerative diseases.

Unlike older reprogramming methods, where skin cells are turned into pluripotent stem cells, known as IPS cells, direct reprogramming means that the skin cells do not pass through the stem cell stage when they are converted into nerve cells. Skipping the stem cell stage probably eliminates the risk of tumours forming when the cells are transplanted. Stem cell research has long been hampered by the propensity of certain stem cells to continue to divide and form tumours after being transplanted.

Before the direct conversion technique can be used in clinical practice, more research is needed on how the new nerve cells survive and function in the brain. The vision for the future is that doctors will be able to produce the brain cells that a patient needs from a simple skin or hair sample. In addition, it is presumed that specifically designed cells originating from the patient would be accepted better by the body’s immune system than transplanted cells from donor tissue.

“This is the big idea in the long run. We hope to be able to do a biopsy on a patient, make dopamine cells, for example, and then transplant them as a treatment for Parkinson’s disease,” says Malin Parmar, who is now continuing the research to develop more types of brain cells using the new technique.

Source: Lund University
Contact: Malin Parmar

Reference:
Direct conversion of human fibroblasts to dopaminergic neurons
Ulrich Pfisterer, Agnete Kirkeby, Olof Torper, James Wood, Jenny Nelander, Audrey Dufour, Anders Björklund, Olle Lindvall, Johan Jakobsson, and Malin Parmar
PNAS 2011; 6 June 2011, doi: 10.1073/pnas.1105135108
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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at
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Stem Cells Help Create Blood Vessel in Life-Saving Surgery

Stem cell technology used in unique surgery of 10-year-old girl Monday, 09 May 2011

A 10-year-old girl with a deadly blood clot underwent a life-saving surgery that showed the power of using stem cells to regenerate healthy organs.

Surgeon and professor Michael

Olausson. Credit: Björn Larsson

Rosvall.

The girl developed a clot in the blood vessel between her intestine and liver during her first year of life, creating the risk of potentially fatal bleeding. Michael Olausson, a surgeon at Sahlgrenska University Hospital at the University of Gothenburg took a blood vessel from a donor, chemically removed tissue and DNA from it, then seeded stem cells from the girl’s bone marrow to create a healthy, living blood vessel.

Surgeon and Professor Michael Olausson were able to create a new connection with the aid of this blood vessel between the liver and the intestines, necessary to cure the girl. The girl is now in good health, and her prognosis is very good. The girl developed during her first year of life a blood clot in the blood vessel that leads blood from the intestines to the liver. This introduced the risk that she would experience life-threatening internal bleeding. The condition can be cured if it is possible to direct the blood along the correct path, back into the liver. In optimal cases, the surgery can be performed using blood vessels from other parts of the patient's body, but a liver transplant may be necessary if the surgery is unsuccessful due to a lack of sufficient blood vessels. A liver transplant will involve subsequent lifelong treatment with immunosuppressive drugs.

Blood vessels from a dead donor were used in the present case. The vessel was then chemically treated to remove all cells RNA and DNA. This left just the supporting tissue. Stem cells were then obtained from the girl's bone marrow and these were added to the supporting tissue. A new blood vessel grew in just under four weeks. This was used during the surgery in order to create the new connection between the liver and the intestines, necessary to cure the girl.

"We carried out the surgery over three months ago now, and the result was very good, with no serious complications. To our knowledge this is the first procedure of this type in the world,” says Michael Olausson.

“The girl is in good health, and we believe that her prognosis is very good. Since the vessel was created with the girl's own stem cells, she does not need to take drugs to prevent rejection", says Michael Olausson at the Transplant Centre, Sahlgrenska University Hospital and professor at the Sahlgrenska Academy.

The procedure shows that it is possible to create new blood vessels from stem cells, using a previous blood vessel as a template. This can lead to the condition that the girl suffered from being treated more easily, and with less risk for the patient. The result of this operation may have implications not only for the condition the girl was suffering from, but also in a number of other fields of research.

"The next step is to intensify research into the recreation of other organs, and to develop methods that can be used for arteries. This can help, among others, patients who need dialysis and those needing surgery for the coronary arteries. It may also help those needing complete organs", says Michael Olausson.

"There may also be major financial benefits for the healthcare system, particularly if it proves possible to produce, for example, complete kidneys by this method, since the consumption of drugs will be dramatically reduced. For the patients, it means that the undesired effects of the drugs that must currently be used will be avoided."

Source: University of Gothenburg
Contact: Michael Olausson
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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/

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