Sheryl Ubelacker, The Canadian Press Published Wednesday, December 10, 2014 1:39PM EST Last Updated Thursday, December 11, 2014 7:42AM EST

TORONTO -- A Canadian-led international team of researchers has begun solving the mystery of just how a specialized cell taken from a person's skin is reprogrammed into an embryonic-like stem cell, from which virtually any other cell type in the body can be generated.

The research is being touted as a breakthrough in regenerative medicine that will allow scientists to one day harness stem cells to treat or even cure a host of conditions, from blindness and Parkinson's disease to diabetes and spinal cord injuries.

Besides creating the reprogramming roadmap, the scientists also identified a new type of stem cell, called an F-class stem cell due to its fuzzy appearance. Their work is detailed in five papers published Wednesday in the prestigious journals Nature and Nature Communications.

Dr. Andras Nagy, a senior scientist at Mount Sinai Hospital in Toronto, led the team of 50 researchers from Canada, the Netherlands, South Korea and Australia, which spent four years analyzing and cataloguing the day-by-day process that occurs in stem cell reprogramming.

The work builds on the 2006-2007 papers by Shinya Yamanaka, who showed that adult skin cells could be turned into embryonic-like, or pluripotent, stem cells through genetic manipulation, a discovery that garnered the Japanese scientist the Nobel Prize in 2012.

Nagy likened the roughly 21-day process to complete that transformation to a "black box," so called because scientists did not know what went on within the cells as they morphed from one cell type into the other.

"It was just like a black box," Nagy said Wednesday, following a briefing at the hospital. "You start with a skin cell, you arrive at a stem cell -- but we had no idea what was happening inside the cell."

Nagy's team set about cataloguing the changes as they occurred by removing cells from culture dishes at set points during the three-week period, then analyzing such cellular material as DNA and proteins present at that moment.

The result is a database that will be available to scientists around the world, which the team hopes will spur new research to advance the field of stem cell-based regenerative medicine.

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Canadian-led team unlocks process to 'reprogram' stem cells

TORONTO A Canadian-led international team of researchers has created the first high-resolution characterization of the process in which stem cells are formulated from other specialized cells.

The research is being touted as a breakthrough in utilizing stem cells to treat or even cure a host of diseases in the future. Certain stem cells have the potential to become any cell type in the body.

Dr. Andras Nagy of Mount Sinai Hospital in Toronto, who led the international research team, says stem cells hold enormous promise for treating or reversing such conditions as blindness, Parkinsons, Alzheimers, spinal cord injury and stroke-related brain damage.

The researchers also identified a new type of stem cells, called F-class stem cells due to their fuzzy appearance.

Nagy says these F-class stem cells have unique properties that could open up new avenues for generating designer cells that may be safer and more efficient when used in future therapies.

Ontario Health Minister Dr. Eric Hoskins hails the research as a game-changer that will open up new frontiers in scientific and medical knowledge worldwide.

The research is detailed in five papers published Wednesday in the prestigious journals Nature and Nature Communications.

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Breakthrough research may speed up stem cell treatments

Marion Welch and Dr. Paul Sanberg

Ridgefielder and cord blood advocate Marion Welch recently met Dr. Paul Sanberg, aneuroscientist and cord blood stem cell researcher and currently distinguished professor at the College of Medicine and Molecular Pharmacology and Physiology at the University of Southern Florida.

Ms. Welch has been educating parents in Connecticut and New York for the past 15 years on preserving cord blood stem cells at the time of birth. She serves as a senior member of Cryo-Cell Internationals field cord blood educator team.

Dr. Sanberg is the author of more than 600 scientific articles and has published 13 books, including Neural Stem Cells: Methods and Protocols and Neural Stem Cells for Brain and Spinal Cord Repair, and is an inventor with more than 100 United States patents. His work is pioneering the clinical use of using cord blood stem cells to treat neurological disorders, Ms. Welch said.

Connecticut has mandated cord blood education for all expectant parents for the last five years.

For more information on cord blood banking, contact Marion Welch at mwelch@cryo-cell.com

For more information on Dr. Sanberg and his research, contact USF Research & Innovation, 3702 Spectrum Blvd., Suite 165, Tampa FL 33612.

Original post:
Cord blood educator meets neuroscientist

Researchers say they've developed a drug that may help heal a damaged spine the first time anything like a drug has been shown to help.

The drug works on nerve cells that are cut, sending connections across the break, and it helped injured rats move their back legs again and also gave them back control of their bladders.

"This recovery is unprecedented," said Jerry Silver, a neuroscience professor at Case Western Reserve University in Ohio who led the study.

Right now, there's no good way to heal a broken spine. Sometimes people grow nerve cells back, but usually not. All the cures that are in the works require invasive surgery, whether it's injections of stem cells, nerve tissue transplants or implants of neurostimulators.

But Silver's team came up with a compound that is injected. It doesn't require surgery.

"We're very excited at the possibility that millions of people could, one day, regain movements lost during spinal cord injuries."

"There are currently no drug therapies available that improve the very limited natural recovery from spinal cord injuries that patients experience," said Lyn Jakeman, a program director at the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, which helped pay for the study. "This is a great step toward identifying a novel agent for helping people recover."

"We're very excited at the possibility that millions of people could, one day, regain movements lost during spinal cord injuries," Silver added.

One of the problems with repairing a crushed spine is scar tissue. The body grows a lot of it, and even if nerve cells try to send out little growths called axons across the breach, they get bogged down by the scar tissue.

The culprits are molecules called proteoglycans. They are covered with sugars, and like anything sugary, they are sticky and grab the delicate axons that nerve cells grow to connect to other nerves. "What we found is that when nerve fibers are damaged they have a receptor that can see those proteoglycan molecules and stick tightly to it. They stick so tightly they can't move. It's like flypaper," Silver told NBC News.

Original post:
'Unprecedented': Drug May Help Heal Damaged Spines

At Stem Cell Treatment Institute advanced stem cell procedures are performed at some of the most scientifically advanced hospitals in the world. Stem cell therapy is focused on affecting physical changes in the Spinal Cord that can improve a patient's quality of life. Spinal Cord Injury patients can be treated by lumbar puncture (injecting the cells into the cerebrospinal fluid), IV, or other techniques. Typically this is an outpatient procedure. however patients may stay for 4 or 5 nights in our suites during the process.

Treatment using autologous (patient source) or donor cells (placenta) are available

If Autologous Bone Marrow is used bone marrow is collected from the patient's iliac crest (hip bone) using thin-needle puncture under local anesthesia. Once the bone marrow collection is complete, patients may return to their suite or hotel and go about normal activities.

The stem cells are then processed in a state-of-the-art laboratory. In the lab, both the quantity and quality of the stem cells are measured. The stem cells are then implanted back into the patient by lumbar puncture or IV.

Cost: Stem cell treatments begin around $13,500 (adults).

To contact us and learn more Click Here >>>

We offer Stem Cell treatments with enhanced or manipulated stem cells. These expanded and mobilized stem cells have been found to provide better results than non-manipulated stem cell applications. Manipulation or amplification of the stem cells is done in the lab, where care is taken to retain the cell properties. These expanded and mobilized cells provide superior results and cell recovery has been found to occur twice as fast as with non-manipulated stem cell applications.

Studies where both types of cells were used show that results were quicker and were obtained predominantly from the manipulated stem cells.

Stem Cells can come from the patients fat or bone marrow, but stem cells from donor placenta or umbilical cord blood is also available and may have improved benefits. Donor characteristics (i.e., age) play a key role in treatment success. Your individual situation will be considered and suitable options will be discussed.

As we age our stem cells become less effective. For this reason younger cells are often preferred. We do not need to go all the way back to an early stage embryo to get young cells. Young cord blood cells can be used from The Placenta, Umbilical Cord, and other young sources. These cord blood cells are more likely than stem cells found in bone marrow to have proliferative properties. This means that stem cells found in cord blood have a greater ability to regenerate.

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Stem Cell Treatment for Spinal Cord Injury

The Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Transplantation in Spinal Cord Injury Patients Location: China

Overview: This trial aims to investigate transplantation of umbilical cord stem cells from patients with paraplegia. The study is being conducted at the General Hospital of Chinese People's Armed Police Forces in Haidian. Stem cells derived from donated umbilical cord blood will be given to the trial participants via the femoral artery. The trial expect to enrol 20 patients with traumatic paraplegia [levels T10 through to L2] between April 2012 and December 2013. Participants will be assessed for complications and for improvement in functions such as bladder contracting capacity as well as sensory responsiveness.

Trial Design: Safety and Efficacy Study

Status: Open - Recruiting

Stem Cell: Umbilical Cord Stem Cells

Intrathecal Transplantation Of Autologous Adipose Tissue Derived MSC in the Patients with Spinal Cord Injury Location: South Korea

Overview: This trial is investigating the effects of stem cells from the patient's own fat in the treatment of chronic spinal cord injury. The trial is being conducted at the Korea University Anam Hospital in Seoul and plans to recruit 15 participants. The fat stem cells will be injected into the fluid surrounding the spinal (intrathecal injection) three times over approximately two months. Participants will be monitored for complications and assessed for changes in neurological and sensory function. The trial is expected to complete in December 2013.

Trial Design: Safety and Efficacy Study

Status: Open - Recruiting

Stem Cell: Adult Fatty Tissue Stem Cells

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Spinal Cord Injury - Stem Cells Australia

Researchers from the University of Dresden have usedembryonic stem cells to grow an intact spinal cord in a petri dish, the team reported this week. Its an enormous achievement in a field that has long viewed neural tissue as the ultimate challenge, and one which could give hope to millions of people suffering fromspinal cord injuries.

Neurons, the cells that form the thinking matrix of your brain and carry its orders to the rest of your body, are very difficult to grow. For a long time growing neurons was thought to be impossible, but then it was discovered that olfactory neurons regrow. This is why you can lose your sense of smell for a few days then slowly regain it; the neuron ends, basically open-ended synapses facing into your nasal cavity, areburned away by corrosive smells, butslowly growback. Intense study followed this discovery, as scientists tried to track down how our olfactory neurons regrow, and others packed them directly into severed spinal cords with real success. In the image above, olfactory neurons have granted a lab rat regains some ability to walk again after being paralyzed (though to be fair, those same researchers are the ones who paralyzed it).

Even if you can grow one, the spinal cord still needs to form connections with an incredible number of body parts.

Now, rather than trying toforceour spinal neurons to act like nasalones, this German teammay have a way of making new ones from scratch. Certain diseases and massive injuries could easily render a spine beyond all hope of repair, but in such a situation a full replacement might still work. Remember, though, that one of the reasons neurons are hard to work with is that they must form complex synaptic connections with other neurons to work properly; just growing the spinal cord is only half the battle, and the patients body still has to accept the new routing hardware and integrate it properly.Still, even just the ability to closelyobserve the growth ofa full spinal cord could move neuronal research forward by leaps and bounds.

This technique worked essentially by letting the stem cells go to work and getting as far out of the way as possible; rather than introducing some novel new growth factor, the researchers basically just created an environment where the spine could grow just like it would in a body. Their setup involved inserting small bubbles of stem cells into a nutrient-rich growth mediumand letting them go from there.Given all the opportunities they required, the cells naturally started coordinating andshuntinggrowth factors around most notably the trio of hedgehog signaling molecules.

The teams diagram shows inserted ESC colonies growing into larger cysts which eventually associate.

The most famous of the three-member band, both for its name and its function, is Sonic Hedgehog, which can stimulate directed neuron growth through itsconcentration gradient. A high concentration of Sonic Hedgehog leads the cord to growmotor neurons tocarry the brains muscular commands, while a lower concentration near the top of the cord will lead to interneurons that wire up the spine itself. This is roughly analogous to growth factors in trees, where the widen the trunk molecule is made at the bottom and ferried up, and the split the trunk into branches molecule is made at the top and ferried down; the two opposing concentration gradients lead to the tree-shaped trees we all know so well, with branches becoming less common toward the bottom, where trunk-width takes priority.

In this case, the stem cells and spinal cord were froma mouse, which allowed for lower cost and ethical considerations, butthe principles of growth and signaling should bethe same. This technique made use of embryonic stem cells (ESCs), which in humans must be collected from fertility clinics and similar, but the ultimate human progenitor cell might not be necessary to further research. As scientists come to understand the mechanics of this breakthrough better, and replicate its results a few more times, it would presumably become possible to begin thisprocesswithinduced stem cells made from adult tissue. If not, this will remain an interesting research tool with little real-world applicabilitydue to the costs and regulatory problemswith ESCs.

Star Trek had a spinal transplant episode but even in the 24th century, its an experimental procedure.

Lab-grown organs are coming far, fast. Somewhere in the world today there are gel baths and petri dishes growing human bladders, eyes, and penises, esophagi, livers, and breasts. Even the quest for lab grown meatfalls under the same basic research umbrella, as scientists use similartechniques to create high quality chicken andbovine skeletal muscle. As with this spinal cord, each of these areas of research is trying to create laboratory conditions that perfectly mimic the body, so cells grow and develop normally.

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Spinal cord has successfully been grown in a lab

I have to admit that my first response to these reports out of Britain that stem cells had been successfully used to repair a complete spinal cord transection was skepticism incredulity even. Theyre reporting that a man with a completely severed spinal cord at level T10-T11 is able to walk again! The Guardian gushes! The Daily Mail gets in the act (always a bad sign)! When I read that the patient had an 8mm gap in his spinal cord that had been filling up with scar tissue for the last two years, I was even more doubtful: under the best of conditions, it was unlikely that youd get substantial connectivity across that distance.

So I read the paper. Im less skeptical now, for a couple of reasons. They actually did this experiment on 3 people, and all showed degrees of improvement, although the newspapers are all focusing on just the one who had the greatest change. The gradual changes are all documented thoroughly and believably. And, sad to say, the improvements in the mans motor and sensory ability are more limited and more realistic than most of the accounts would have you think.

The story is actually in accord with what weve seen in stem cell repair of spinal cord injury in rats and mice.

Overall, they found that stem cell treatment results in an average improvement of about 25% over the post-injury performance in both sensory and motor outcomes, though the results can vary widely between animals. For sensory outcomes the degree of improvement tended to increase with the number of cells introduced scientists are often reassured by this sort of dose response, as it suggests a real underlying biologically plausible effect. So the good news is that stem cell therapy does indeed seem to confer a statistically significant improvement over the residual ability of the animals both to move and feel things beyond the spinal injury site.

Significant but far from complete improvement is exactly what wed expect, and that improvement is a very, very good thing. It is an accomplishment to translate animal studies into getting measurable clinical improvements in people.

The basic procedure is straightforward. There is a population of neural cells in humans that do actively and continuously regenerate: the cells of the olfactory bulb. So what they did is remove one of the patients own olfactory bulbs, dissociate it into a soup of isolated cells, and inject them into locations above and below the injury. They also bridged the gap with strips of nerve tissue harvested from the patients leg. The idea is that the proliferating cells and the nerves would provide a nerve growth-friendly environment and build substrate bridges that would stimulate the damaged cells and provide a path for regrowth.

Big bonus: this was an autologous transplant (from the patients own tissues), so there was no worry about immune system rejection. There were legitimate worries about inflammation, doing further damage to the spinal cord, and provoking greater degeneration, and part of the purpose of this work was to assess the safety of the procedure. There were no complications.

Also, Im sure you were worried about this, but the lost olfactory cells also regenerated and the patients completely recovered their sense of smell.

Now heres the clinical assessment. Three patients were operated on; T1 is the one who has made all the news with the most remarkable improvement. There were also three control patients who showed no improvement over the same period.

Neurological function improved in all three transplant recipients (T1, T2, T3) during the first year postsurgery. This included a decrease of muscle spasticity (T1, T2) as well as improvement of sensory (T1, T2, T3) and motor function (T1, T2, T3) below the level of spinal cord injury.

Read this article:
Stem cell treatment of spinal cord injuries

A young man that was paralyzed after a gunshot wound to the spine, and after 4 weeks of stem cell treatment he regained use of his legs. We look at video of his recovery and speak with his doctor, Dr. Neil Riordan about the treatment and the potential rewards--both medical and emotional--of stem cell treatment in this excerpt from the Lip News interview, hosted by Elliot Hill. Watch the full length Lip News interview here: https://www.youtube.com/watch?v=7qpqf...

http://www.thelip.tv

Newest Lip News playlist: https://www.youtube.com/watch?v=_nj-C...

BUZZSAW interview clips - https://www.youtube.com/watch?v=WRyNW...

CRIME TIME clips playlist - https://www.youtube.com/watch?v=wSwaJ...

BYOD (Bring Your Own Doc) Highlight Videos- https://www.youtube.com/watch?v=yJ_3Q...

MEDIA MAYHEM short videos playlist - https://www.youtube.com/watch?v=YyUpK...

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Stem Cells Help Victim of Spinal Cord Injury to Walk

11 hours ago Neurons (green) are detected by TuJI whereas motoneurons are revealed in red by the visicular transporter of acetylcholine. Credit: Inserm/Martinat, Ccile

The motor neurons that innervate muscle fibres are essential for motor activity. Their degeneration in many diseases causes paralysis and often death among patients. Researchers at the Institute for Stem Cell Therapy and Exploration of Monogenic Diseases (I-Stem - Inserm/AFM/UEVE), in collaboration with CNRS and Paris Descartes University, have recently developed a new approach to better control the differentiation of human pluripotent stem cells, and thus produce different populations of motor neurons from these cells in only 14 days. This discovery, published in Nature Biotechnology, will make it possible to expand the production process for these neurons, leading to more rapid progress in understanding diseases of the motor system, such as infantile spinal amyotrophy or amyotrophic lateral sclerosis (ALS).

Human pluripotent stem cells have the ability to give rise to every cell in the body. To understand and control their potential for differentiation in vitro is to offer unprecedented opportunities for regenerative medicine and for advancing the study of physiopathological mechanisms and the quest for therapeutic strategies. However, the development and realisation of these clinical applications is often limited by the inability to obtain specialised cells such as motor neurons from human pluripotent stem cells in an efficient and targeted manner. This inefficiency is partly due to a poor understanding of the molecular mechanisms controlling the differentiation of these cells.

Inserm researchers at the Institute for Stem Cell Therapy and Exploration of Monogenic Diseases (I-Stem - Inserm/French Muscular Dystrophy Association [AFM]/University of vry Val d'Essonne [UEVE]), in collaboration with CNRS and Paris-Descartes University, have developed an innovative approach to study the differentiation of human stem cells and thus produce many types of cells in an optimal manner.

"The targeted differentiation of human pluripotent stem cells is often a long and rather inefficient process. This is the case when obtaining motor neurons, although these are affected in many diseases. Today, we obtain these neurons with our approach in only 14 days, nearly twice as fast as before, and with a homogeneity rarely achieved," explains Ccile Martinat, an Inserm Research Fellow at I-Stem.

To achieve this result, the researchers studied the interactions between some molecules that control embryonic development. These studies have made it possible to both better understand the mechanisms governing the generation of these neurons during development, and develop an optimal "recipe" for producing them efficiently and rapidly.

"We are now able to produce and hence study different populations of neurons affected to various degrees in diseases that cause the degeneration of motor neurons. We plan to study why some neurons are affected and why others are preserved," adds Stphane Nedelec, an Inserm researcher in Ccile Martinat's team.

In the medium term, the approach should contribute to the development of treatments for paralytic diseases such as infantile spinal muscular amyotrophy or amyotrophic lateral sclerosis. "Rapid access to large quantities of neurons will be useful for testing a significant number of pharmacological drugs in order to identify those capable of preventing the death of motor neurons," concludes Ccile Martinat.

Explore further: Team finds a better way to grow motor neurons from stem cells

More information: Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes, Nature Biotechnology, 17 Nov 2014. DOI: 10.1038/nbt.3049

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Production of human motor neurons from stem cells gaining speed

For more than 30 years, stem cells have been the great hope of medical science. Given their remarkable ability to turn into any type of cell in the body, researchers have theorized that they could be used to treat and perhaps even cure all sorts of diseases and conditions from spinal cord injury to baldness.

Progress has been painfully slow for most areas of research but this week researchers in Sweden are reporting a major advancein a possible stem cell treatment for Parkinson's. While the treatment has only been tried in rats, the scientists -- led byMalin Parmar, an associate professor of regenerative neurobiology at the Lund University -- said they believe the results are promising enoughto move to clinical trials in humans within a few years.

A degenerative condition of the central nervous system, Parkinson's affects an estimated 7 to 10 million people worldwide -- including actor Michael J. Fox and Google co-founder Sergey Brin, both of whom have not only raised awareness of the disease through their celebrity but have contributed millions of dollars to advance research.

Parkinson's is caused by the loss of dopamine-producing cells in the brain that help regulate things like movement and emotions. The scientistsat the Lund University found that when they turned human embryonic stem cells into neurons that produce dopamine and injected them into the brains of rats, something remarkable happened. The damage from the disease seemed to reverse.

The scientists wrote that while they believe their research was "rigorous," they pointed out that "a number of crucial issues" still need to be addressed before the treatment can be tested in humans. For instance, they need to make sure the cells continue to work the way are supposed to over longer time periods.

Ariana Eunjung Cha is a national reporter for the Post. She has previously served as the newspapers bureau chief in Beijing, Shanghai and San Francisco, a correspondent in Baghdad and as a tech reporter based in Washington.

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New hope for Parkinsons patients in stem cell treatment

16 hours ago

Researchers at the University of Cambridge have managed to reconstruct the early stage of mammalian development using embryonic stem cells, showing that a critical mass of cells not too few, but not too many is needed for the cells to being self-organising into the correct structure for an embryo to form.

All organisms develop from embryos: a cell divides generating many cells. In the early stages of this process, all cells look alike and tend to aggregate into a featureless structure, more often than not a ball. Then, the cells begin to 'specialise' into different types of cell and space out asymmetrically, forming an axis which begins to provide a structure for the embryo to develop along.

In animal embryos this stage is followed by a process known as gastrulation: a choreographed movement of the cells that, using the initial axis as a reference, positions the head and the tail, the front and the back. During the process, the cells begin to forum three distinct layers: the endoderm, mesoderm and ectoderm, determining which tissues or organs the cells will then develop into.

Professor Alfonso Martinez-Arias from the Department of Genetics at the University of Cambridge, who led the research, says: "Gastrulation was described by biologist Professor Lewis Wolpert as being 'truly the most important event in your life' because it creates the blueprint of an organism. Axis formation and gastrulation are the two central processes that initiate the development of an organism and are inextricably associated with the embryo. We have managed to recreate this for the first time in the lab."

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Professor Martinez-Arias and colleagues, supported by the European Research Council and the Wellcome Trust, have reconstructed these early stages of development using mouse embryonic stem cells. Embryonic stem cells, discovered in the Department of Genetics in the 1980s (for which Sir Martin Evans was awarded the Nobel Prize in Physiology or Medicine 2007), have become an important tool for developmental biology, understanding disease, and in regenerative medicine due to the ability to give rise to all cell types in culture. Over the last few years, they have been used to 'grow' organs including the eye and the cerebral cortex; surprisingly, these structures develop without an axis.

In research published today in the journal Development, the researchers report a way to coax cells to reorganize in the manner that they do in an embryo, creating an axis and undergoing movements and organisations that mimic the process of gastrulation. Over the years researchers have been making aggregates of embryonic stem cells to obtain certain cell types, for example red blood cells. However, these aggregates lack structure and the different cell types emerge in a disorganised fashion. This is the first time that researchers have been able to elicit axis formation, spatial organisation and gastrulation-like movements from aggregates of embryonic stem cells.

The researchers show that if the number of cells aggregated initially is similar to that of a mouse embryo, the cells generate a single axis and this serves as a template for a sequence of events that mimics those of the early embryo. By manipulating the signals that the cells see at a particular time, the researchers were able to influence what type of cell they become and how they are organised. In one of the experiments, for example, activation of a particular signal at the correct time elicits the appearance of the mesoderm, endoderm and ectoderm the precursors of all cell types with a spatial organization similar to that of an embryo.

Using this experimental system, the researchers were able to generate the early stages of a spinal cord, which they showed forms as part of the process of gastrulation. This finding complements previous research from the University of Edinburgh and the National Institute for Medical Research which showed that embryonic stem cells can be coaxed into this spinal cord cells; however, the Cambridge researchers showed that the in the embryo-like aggregates, the structural organization is more robust and allows for the polarised growth of the tissue.

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Researchers reconstruct early stages of embryo development

PUBLIC RELEASE DATE:

4-Nov-2014

Contact: Craig Brierley craig.brierley@admin.cam.ac.uk 44-012-237-66205 University of Cambridge @Cambridge_Uni

Researchers at the University of Cambridge have managed to reconstruct the early stage of mammalian development using embryonic stem cells, showing that a critical mass of cells not too few, but not too many is needed for the cells to being self-organising into the correct structure for an embryo to form.

All organisms develop from embryos: a cell divides generating many cells. In the early stages of this process, all cells look alike and tend to aggregate into a featureless structure, more often than not a ball. Then, the cells begin to 'specialise' into different types of cell and space out asymmetrically, forming an axis which begins to provide a structure for the embryo to develop along.

In animal embryos this stage is followed by a process known as gastrulation: a choreographed movement of the cells that, using the initial axis as a reference, positions the head and the tail, the front and the back. During the process, the cells begin to forum three distinct layers: the endoderm, mesoderm and ectoderm, determining which tissues or organs the cells will then develop into.

Professor Alfonso Martinez-Arias from the Department of Genetics at the University of Cambridge, who led the research, says: "Gastrulation was described by biologist Professor Lewis Wolpert as being 'truly the most important event in your life' because it creates the blueprint of an organism. Axis formation and gastrulation are the two central processes that initiate the development of an organism and are inextricably associated with the embryo. We have managed to recreate this for the first time in the lab."

Professor Martinez-Arias and colleagues, supported by the European Research Council and the Wellcome Trust, have reconstructed these early stages of development using mouse embryonic stem cells. Embryonic stem cells, discovered in the Department of Genetics in the 1980s (for which Sir Martin Evans was awarded the Nobel Prize in Physiology or Medicine 2007), have become an important tool for developmental biology, understanding disease, and in regenerative medicine due to the ability to give rise to all cell types in culture. Over the last few years, they have been used to 'grow' organs including the eye and the cerebral cortex; surprisingly, these structures develop without an axis.

In research published today in the journal Development, the researchers report a way to coax cells to reorganize in the manner that they do in an embryo, creating an axis and undergoing movements and organisations that mimic the process of gastrulation. Over the years researchers have been making aggregates of embryonic stem cells to obtain certain cell types, for example red blood cells. However, these aggregates lack structure and the different cell types emerge in a disorganised fashion. This is the first time that researchers have been able to elicit axis formation, spatial organisation and gastrulation-like movements from aggregates of embryonic stem cells.

The researchers show that if the number of cells aggregated initially is similar to that of a mouse embryo, the cells generate a single axis and this serves as a template for a sequence of events that mimics those of the early embryo. By manipulating the signals that the cells see at a particular time, the researchers were able to influence what type of cell they become and how they are organised. In one of the experiments, for example, activation of a particular signal at the correct time elicits the appearance of the mesoderm, endoderm and ectoderm the precursors of all cell types with a spatial organization similar to that of an embryo.

Original post:
Shaping up: Researchers reconstruct early stages of embryo development

The central nervous system in vertebrates develops from the neural tube, which is the basis for the differentiation in spinal cord and brain. Professor Elly Tanaka and her research group at the DFG Research Center for Regenerative Therapies Dresden -- Cluster of Excellence at the TU Dresden (CRTD) demonstrated for the first time the in vitro growth of a piece of spinal cord in three dimensions from mouse embryonic stem cells. Correct spatial organization of motor neurons, interneurons and dorsal interneurons along the dorsal/ventral axis was observed. This study has been published online by the American journal Stem Cell Reports.

For many years Elly Tanaka and her research group have been studying the regenerative potential of axolotls at the molecular level. The Mexican salamanders have the potential to regenerate their spinal cord and other organs to restore full functionality after injury. Mammals such as humans are not able to regenerate most organs. The restoration of the spinal cord in axolotl occurs in a three dimensional structure similar to an embryonic spinal cord. Due to their positions in the tissue, cells in the regenerated spinal cord know which function to perform in the restored tissue. "In this study we applied the knowledge gained about the regenerative potential in axolotls to a mammal, the mouse" explains Professor Elly Tanaka.

Single mouse embryonic stem cells embedded in a three-dimensional matrix and were grown in neural differentiation medium led to the clonal development of neuroepithelial cysts. These cysts settled in the midbrain and hindbrain along the neural axis. "Our goal, however, was to generate spinal cord in vitro," says Dr. Andrea Meinhardt, a postdoc at the CRTD. "For this reason we added retinoic acid to the culture medium on the second day of the 3D cell culture." The result not only caused the neural tissue to switch to spinal cord but also induced the formation of a local signaling center for forming all the different cell types of the spinal cord. "For the first time we could hereby reconstruct the structure of a typical embryonic neural tube in vitro," said Andrea Meinhardt.

"With this study we have moved a tiny step closer to turn the idea of constructing a three-dimensional piece of spinal cord for transplantation in humans into reality" says Elly Tanaka.

Story Source:

The above story is based on materials provided by Technische Universitaet Dresden. Note: Materials may be edited for content and length.

Continued here:
Reconstruction of patterned piece of spinal cord in 3D culture

In 2010, Darek Fidyka was paralyzed from the chest down as a result of a knife attack that left an 8 mm gap in his spinal column. Now surgeons in Poland, working in collaboration with scientists in London, have given Fidyka the ability to walk again thanks to a new procedure using transplanted cells from his olfactory bulbs.

The spinal injury that left Darek Fidyka paralyzed did not see the spinal cord entirely severed, but rather an 8 mm chunk removed from the left side. Researchers have for years worked to develop treatments to help those with spinal injuries, but for Fidyka no amount of therapy was helping him recover feeling below his chest. Now, two years after the groundbreaking treatment, Fidyka has regained some feeling in his legs, feet, bowels, bladder, and can now walk with the assistance of a frame.

The procedure saw the medical team remove one of Fidykas olfactory bulbs then grow olfactory ensheathing cells (OECs) in culture and graft the cells onto his damaged spinal column where they helped to re-link vital nerve fibers. According to the UCL, the OECs act as pathway cells that repair and renew nerve fibers when damaged. The team chose OECs as they are the only part of the nervous system with the ability to regenerate in adults.

A few weeks after the initial OEC removal and culture harvesting, the team applied 100 micro-injections of the olfactory cells above and below the injured area. Then four thin strips of nerve tissue from Fidykas ankle were applied across the damaged area. After about three months they noticed muscle mass increasing on his left thigh, and after six months Fidyka was able to stand and take his first steps with the assistance of parallel bars, leg braces and a physiotherapist. Today he still undergoes five hours of physiotherapy, five days a week.

"It is immensely gratifying to see that years of research have now led to the development of a safe technique for transplanting cells into the spinal cord." said Professor Geoff Raisman, Chair of Neural Regeneration at the UCL Institute of Neurology. "I believe we stand on the threshold of a historic advance and that the continuation of our work will be of major benefit to mankind. I believe we have now opened the door to a treatment of spinal cord injury that will get patients out of wheel chairs. Our goal now is to develop this first procedure to a point where it can be rolled out as a worldwide general approach."

The BBC Panorama program To Walk Again shows the procedure and footage of Fidyka walking with a frame. When asked what it was like to walk again, Fidyka said, "when you cant feel almost half your body, you are helpless, but when it starts coming back its as if you were born again."

The treatment marks a world first in cell transplantation and paralysis reversal. The project was jointly funded by the Nicholls Spinal Injury Foundation and the UK Stem Cell Foundation. Professor Raisman, who first discovered OECs in 1985, went on to show how the treatment could be applied on rats with spinal injuries in 1997.

Details of the research can be found in the journal Cell Transplantation.

Sources: UCL Institute of Neurology, BBC Panorama

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Cell transplant enables paralyzed man to walk again

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ALBUQUERQUE, N.M. A man paralyzed from the chest down in a knife attack is walking again after undergoing surgery using cells responsible for the sense of smell, marking an advance in the search for treatments for spinal injuries.

Darek Fidyka, 38, received the cells after failing to recover from a stabbing in the back in 2010, according to University College London, whose doctors developed the procedure. The technique involves using olfactory ensheathing cells and placing them in the spinal cord.

The study gives hope to the thousands of people each year who suffer a severe spinal cord injury and must live the rest of their lives with permanently damaged body functions. Such injuries typically occur during sports or automobile crashes and there is no approved treatment to repair them.

We have now opened the door to a treatment of spinal cord injury that will get patients out of wheelchairs, said Geoff Raisman, chairman of neural regeneration at the UCL Institute of Neurology and leader of the U.K. research team. Our goal now is to develop this first procedure to a point where it can be rolled out as a worldwide general approach.

The cells used were discovered by Raisman in 1985 and were shown to work in treating spinal injuries in rats in 1997. They allow nerve cells that give people their sense of smell to grow back when they are damaged. The procedure on Fidyka was performed by surgeons at Wroclaw University Hospital in Poland.

For the treatment, Fidyka underwent brain surgery to remove an olfactory bulb, a structure responsible for the sense of smell. The bulb was placed in a cell culture for two weeks to produce olfactory cells, which were injected into the spinal cord along with four strips of nerve tissue taken from the ankle. The strips formed bridges for the spinal nerve fibers to grow across, with the aid of the cells.

Three months after the surgery, Fidykas left thigh muscle began to grow and after six months he was starting to walk within the rehabilitation center with the help of a physiotherapist and leg braces, according to UCL. His bladder sensation and sexual function have also improved.

The research, funded by the UK Stem Cell Foundation and the Nicholls Spinal Injury Foundation, was published in the Cell Transplantation journal. Further studies in patients are planned.

Its as if you were born again, the patient, who can now walk using a walker, said in a statement from University College London.

See original here:
Man walks again after nose cells put in spine

A man completely paralysed from the waist down after his spinal cord was sliced in half in a stabbing is able to walk again after undergoing pioneering surgery.

Darek Fidyka, who suffered the injury in 2010, is believed to be the first person in the world to recover from complete severing of the spinal nerves.

The 40-year-old Pole can now walk with a frame and has been able to resume an independent life, even to the extent of driving a car. Sensation has returned to his lower limbs.

Surgeons used nerve-supporting cells from Mr Fidykas nose to provide pathways along which the broken tissue was able to grow.

Despite laboratory success, it is the first time the procedure has worked in a human patient.

Geoffrey Raisman, whose team at University College Londons Institute of Neurology discovered the technique, said: We believe that this procedure is the breakthrough which, as it is further developed, will result in a historic change in the currently hopeless outlook for people disabled by spinal cord injury.

The research, funded by the Nicholls Spinal Injury Foundation and the UK Stem Cell Foundation, will be featured in a special Panorama programme on BBC One tonight.

A Polish team led by one of the worlds top spinal repair experts, Pawel Tabakow, from Wroclaw Medical University, performed the surgery.

The procedure involved transplanting olfactory ensheathing cells (OECs) from the nose to the spinal cord.

OECs assist the repair of damaged nerves that transmit smell messages by opening up pathways for them to the olfactory bulbs in the forebrain.

Continued here:
Severed spinal cord regrown with nose cells

I have to admit that my first response to these reports out of Britain that stem cells had been successfully used to repair a complete spinal cord transection was skepticism incredulity even. Theyre reporting that a man with a completely severed spinal cord at level T10-T11 is able to walk again! The Guardian gushes! The Daily Mail gets in the act (always a bad sign)! When I read that the patient had an 8mm gap in his spinal cord that had been filling up with scar tissue for the last two years, I was even more doubtful: under the best of conditions, it was unlikely that youd get substantial connectivity across that distance.

So I read the paper. Im less skeptical now, for a couple of reasons. They actually did this experiment on 3 people, and all showed degrees of improvement, although the newspapers are all focusing on just the one who had the greatest change. The gradual changes are all documented thoroughly and believably. And, sad to say, the improvements in the mans motor and sensory ability are more limited and more realistic than most of the accounts would have you think.

The story is actually in accord with what weve seen in stem cell repair of spinal cord injury in rats and mice.

Overall, they found that stem cell treatment results in an average improvement of about 25% over the post-injury performance in both sensory and motor outcomes, though the results can vary widely between animals. For sensory outcomes the degree of improvement tended to increase with the number of cells introduced scientists are often reassured by this sort of dose response, as it suggests a real underlying biologically plausible effect. So the good news is that stem cell therapy does indeed seem to confer a statistically significant improvement over the residual ability of the animals both to move and feel things beyond the spinal injury site.

Significant but far from complete improvement is exactly what wed expect, and that improvement is a very, very good thing. It is an accomplishment to translate animal studies into getting measurable clinical improvements in people.

The basic procedure is straightforward. There is a population of neural cells in humans that do actively and continuously regenerate: the cells of the olfactory bulb. So what they did is remove one of the patients own olfactory bulbs, dissociate it into a soup of isolated cells, and inject them into locations above and below the injury. They also bridged the gap with strips of nerve tissue harvested from the patients leg. The idea is that the proliferating cells and the nerves would provide a nerve growth-friendly environment and build substrate bridges that would stimulate the damaged cells and provide a path for regrowth.

Big bonus: this was an autologous transplant (from the patients own tissues), so there was no worry about immune system rejection. There were legitimate worries about inflammation, doing further damage to the spinal cord, and provoking greater degeneration, and part of the purpose of this work was to assess the safety of the procedure. There were no complications.

Also, Im sure you were worried about this, but the lost olfactory cells also regenerated and the patients completely recovered their sense of smell.

Now heres the clinical assessment. Three patients were operated on; T1 is the one who has made all the news with the most remarkable improvement. There were also three control patients who showed no improvement over the same period.

Neurological function improved in all three transplant recipients (T1, T2, T3) during the first year postsurgery. This included a decrease of muscle spasticity (T1, T2) as well as improvement of sensory (T1, T2, T3) and motor function (T1, T2, T3) below the level of spinal cord injury.

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Stem cell treatment of spinal cord injuries [Pharyngula]

A man paralysed from the waist down after his spinal cord was sliced in half in a stabbing attack is able to walk again thanks to cells transplanted from his NOSE.

Darek Fidyka, 38, is believed to be the first person in the world to recover from complete severing of the spinal nerves.

The Bulgarian - who suffered his injury in 2010 - can now walk with a frame and has been able to resume an independent life, even to the extent of driving a car.

Sensation has returned to his lower limbs.

Surgeons used nerve-supporting cells from Darek's nose to provide pathways along which the broken tissue was able to grow.

Despite success in the laboratory, it is the first time the procedure has been shown to work in a human patient.

Professor Geoffrey Raisman, whose team at University College London's Institute of Neurology discovered the technique, said: "We believe that this procedure is the breakthrough which, as it is further developed, will result in a historic change in the currently hopeless outlook for people disabled by spinal cord injury."

The research, funded by the Nicholls Spinal Injury Foundation (NSIF) and the UK Stem Cell Foundation, is featured in a special Panorama programme on BBC One tonight.

A Polish team led by one of the world's top spinal repair experts, Dr Pawel Tabakow, from Wroclaw Medical University, performed the surgery.

Here is the original post:
Paralysed man able to walk again thanks to cells transplanted from his NOSE

A man paralyzed from the chest down in a knife attack is walking again after undergoing surgery using cells responsible for the sense of smell, marking an advance in the search for treatments for spinal injuries.

Darek Fidyka, 38, received the cells after failing to recover from a stabbing in the back in 2010, according to University College London, whose doctors developed the procedure. The technique involves using olfactory ensheathing cells and placing them in the spinal cord.

The study gives hope to the thousands of people each year who suffer a severe spinal cord injury and must live the rest of their lives with permanently damaged body functions. Such injuries typically occur during sports or automobile crashes and there is no approved treatment to repair them.

We have now opened the door to a treatment of spinal cord injury that will get patients out of wheelchairs, said Geoff Raisman, chairman of neural regeneration at the UCL Institute of Neurology and leader of the U.K. research team. Our goal now is to develop this first procedure to a point where it can be rolled out as a worldwide general approach.

The cells used were discovered by Raisman in 1985 and were shown to work in treating spinal injuries in rats in 1997. They allow nerve cells that give people their sense of smell to grow back when they are damaged. The procedure on Fidyka was performed by surgeons at Wroclaw University Hospital in Poland.

For the treatment, Fidyka underwent brain surgery to remove an olfactory bulb, a structure responsible for the sense of smell. The bulb was placed in a cell culture for two weeks to produce olfactory cells, which were injected into the spinal cord along with four strips of nerve tissue taken from the ankle. The strips formed bridges for the spinal nerve fibers to grow across, with the aid of the cells.

Three months after the surgery, Fidykas left thigh muscle began to grow and after six months he was starting to walk within the rehabilitation center with the help of a physiotherapist and leg braces, according to UCL. His bladder sensation and sexual function have also improved.

This technology has been confined to labs, so its promising to see that it may have helped someone recover from a clean cut through the spinal cord, said Jeremy Fairbank, a professor of spine surgery at the University of Oxford who wasnt involved in the research.

The next question is what sort of clinical experiments must be done to prove that this works, Fairbank said. I suspect it will take years until there is a practical way of doing this.

The research, funded by the UK Stem Cell Foundation and the Nicholls Spinal Injury Foundation, was published in the Cell Transplantation journal. Further studies in patients are planned by UCL and Wroclaw University Hospital, according to Michael Hanna, director of the UCL Institute of Neurology.

Continued here:
Paralyzed Man Walks Again After Nose Cells Are Placed in Spine