Durham, NC (PRWEB) August 22, 2014

Human induced pluripotent stem cells (hiPSCs) have great potential in the field of regenerative medicine because they can be coaxed to turn into specific cells; however, the new cells dont always act as anticipated. They sometimes mutate, develop into tumors or produce other negative side effects. But in a new study recently published in STEM CELLS Translational Medicine, researchers appear to have found a way around this, simply by removing the material used to reprogram the stem cell after they have differentiated into the desired cells.

The study, by Ken Igawa, M.D., Ph.D., and his colleagues at Tokyo Medical and Dental University along with a team from Osaka University, could have significant implications both in the clinic and in the lab.

Scientists induce (differentiate) the stem cells to become the desired cells, such as those that make up heart muscle, in the laboratory using a reprogramming transgene that is, a gene taken from one organism and introduced into another using artificial techniques.

We generated hiPSC lines from normal human skin cells using reprogramming transgenes, then we removed the reprogramming material. When we compared the transgene-free cells with those that had residual transgenes, both appeared quite similar, Dr. Igawa explained. However, after the cells differentiation into skin cells, clear differences were observed.

Several types of analyses revealed that the keratinocytes cells that make up 90 percent of the outermost skin layer that emerged from the transgene-free hiPSC lines were more like normal human cells than those coming from the hiPSCs that still contained some reprogramming material.

These results suggest that transgene-free hiPSC lines should be chosen for therapeutic purposes, Dr. Igawa concluded.

Human induced pluripotent stem cell (hiPSC) lines have potential for therapeutics because of the customized cells and organs that can potentially be induced from such cells, Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. This study illustrates a potentially powerful approach for creating hiPSCs for clinical use.

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The full article, Removal of Reprogramming Transgenes Improves the Tissue Reconstitution Potential of Keratinocytes Generated From Human Induced Pluripotent Stem Cells, can be accessed at http://stemcellstm.alphamedpress.org/content/early/2014/07/14/sctm.2013-0179.abstract.

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Removing Programming Material After Inducing Stem Cells Could Improve Their Regeneration Ability

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Newswise A genetic variation linked to schizophrenia, bipolar disorder and severe depression wreaks havoc on connections among neurons in the developing brain, a team of researchers reports. The study, led by Guo-li Ming, M.D., Ph.D., and Hongjun Song, Ph.D., of the Johns Hopkins University School of Medicine and described online Aug. 17 in the journal Nature, used stem cells generated from people with and without mental illness to observe the effects of a rare and pernicious genetic variation on young brain cells. The results add to evidence that several major mental illnesses have common roots in faulty wiring during early brain development.

This was the next best thing to going back in time to see what happened while a person was in the womb to later cause mental illness, says Ming. We found the most convincing evidence yet that the answer lies in the synapses that connect brain cells to one another.

Previous evidence for the relationship came from autopsies and from studies suggesting that some genetic variants that affect synapses also increase the chance of mental illness. But those studies could not show a direct cause-and-effect relationship, Ming says.

One difficulty in studying the genetics of common mental illnesses is that they are generally caused by environmental factors in combination with multiple gene variants, any one of which usually could not by itself cause disease. A rare exception is the gene known as disrupted in schizophrenia 1 (DISC1), in which some mutations have a strong effect. Two families have been found in which many members with the DISC1 mutations have mental illness.

To find out how a DISC1 variation with a few deleted DNA letters affects the developing brain, the research team collected skin cells from a mother and daughter in one of these families who have neither the variation nor mental illness, as well as the father, who has the variation and severe depression, and another daughter, who carries the variation and has schizophrenia. For comparison, they also collected samples from an unrelated healthy person. Postdoctoral fellow Zhexing Wen, Ph.D., coaxed the skin cells to form five lines of stem cells and to mature into very pure populations of synapse-forming neurons.

After growing the neurons in a dish for six weeks, collaborators at Pennsylvania State University measured their electrical activity and found that neurons with the DISC1 variation had about half the number of synapses as those without the variation. To make sure that the differences were really due to the DISC1 variation and not to other genetic differences, graduate student Ha Nam Nguyen spent two years making targeted genetic changes to three of the stem cell lines.

In one of the cell lines with the variation, he swapped out the DISC1 gene for a healthy version. He also inserted the disease-causing variation into one healthy cell line from a family member, as well as the cell line from the unrelated control. Sure enough, the researchers report, the cells without the variation now grew the normal amount of synapses, while those with the inserted mutation had half as many.

We had our definitive answer to whether this DISC1 variation is responsible for the reduced synapse growth, Ming says.

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Stem Cells Reveal How Illness-Linked Genetic Variation Affects Neurons

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Newswise Hematopoietic stem cells (HSCs) give rise to all other blood cell types, but their development and how their fate is determined has long remained a mystery. In a paper published online this week in Nature, researchers at the University of California, San Diego School of Medicine elaborate upon a crucial signaling pathway and the role of key proteins, which may help clear the way to generate HSCs from human pluripotent precursors, similar to advances with other kinds of tissue stem cells.

Principal investigator David Traver, PhD, professor in the Department of Cellular and Molecular Medicine, and colleagues focused on the Notch signaling pathway, a system found in all animals and known to be critical to the generation of HSCs in vertebrates. Notch signaling between emitting and receiving cells is key to establishing HSC fate during development, said Traver. What has not been known is where, when and how Notch signal transduction is mediated.

Traver and colleagues discovered that the Notch signal is transduced into HSC precursor cells from signal emitting cells in the somite embryologic tissues that eventually contribute to development of major body structures, such as skeleton, muscle and connective tissues much earlier in the process than previously anticipated.

More specifically, they found that JAM proteins, best known for helping maintain tight junctions between endothelial cells to prevent vascular leakage, were key mediators of Notch signaling. When the researchers caused loss of function in JAM proteins in a zebrafish model, Notch signaling and HSCs were also lost. When they enforced Notch signaling through other means, HSC development was rescued.

To date, it has not been possible to generate HSCs de novo from human pluripotent precursors, like induced pluripotent stem cells, said Traver. This has been due in part to a lack of understanding of the complete set of factors that the embryo uses to make HSCs in vivo. It has also likely been due to not knowing in what order each required factor is needed.

Our studies demonstrate that Notch signaling is required much earlier than previously thought. In fact, it may be one of the earliest determinants of HSC fate. This finding strongly suggests that in vitro approaches to instruct HSC fate from induced pluripotent stem cells must focus on the Notch pathway at early time-points in the process. Our findings have also shown that JAM proteins serve as a sort of co-receptor for Notch signaling in that they are required to maintain close contact between signal-emitting and signal-receiving cells to permit strong activation of Notch in the precursors of HSCs.

The findings may have far-reaching implications for eventual development of hematopoietic stem cell-based therapies for diseases like leukemia and congenital blood disorders. Currently, it is not possible to create HSCs from differentiation of embryonic stem cells or induced pluripotent stem cells pluripotent cells artificially derived from non-pluripotent cells, such as skin cells that are being used in other therapeutic research efforts.

Co-authors include Isao Kobayashi, Jingjing Kobayashi-Sun, Albert D. Kim and Claire Pouget, UC San Diego Department of Cellular and Molecular Medicine; Naonobu Fujita, UC San Diego Section of Cell and Developmental Biology; and Toshio Suda, Keio University, Japan.

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New Blood: Tracing the Beginnings of Hematopoietic Stem Cells

TO SOME people, the term stem cell may seem kind of taboo. I personally would not want something from animals injected into my system. But Im okay with non-invasive treatments, so I was interested to try out a plant-based stem cell facial.

After cleansing and toning, cotton pads moistened with a clear solution were laid on my eyelids to protect them from a three-minute steaming session. This was followed by a special tool called a scrubber that kind of looks like a computer mouse, but helps to remove dead skin cells and unblock pores without using the rather painful pricking tool.

Next, a rejuvenating gel was applied, followed by the plant-derived stem cell formula. A unique cooling machine was used to massage it into the skin for 10 minutes. Using this machine for cold electrophoresis helps the skin absorb serums and vitamins, without having to use injections. This was great for someone like me, who is wary of invasive treatments. The cooling machine feels like having an ice-cold metal ball massaged on the face; very invigorating, indeed.

Just when I thought my skin already got a lot of pampering, the stem cell was followed by a face mask full of natural vitamins. While it penetrated into my skin, I was given an arm and foot massage, which was nice for further relaxation.

With my combination skin, I looked pretty greasy right afterwards. When I woke up the next day, I didnt see a visible difference in my skin, but it was very smooth and supple to the touch. You may not see instant results with a treatment like this, but its a good treatment to maintain radiance, softness and hydration from beneath the surface of the skin.

This type of facial is not recommended for those with oily or acne-prone skin because the added oiliness may exacerbate problems, but it is ideal for those with dry or mature skin, as it is deeply nourishing and moisturizing. After the first treatment or over time, depending on the condition of your skin, stem cell diminishes fine lines, prevents wrinkles, and promotes cell renewal (a process that slows with age) to give that glowing look that signifies healthy, youthful skin.

I tried out the stem cell facial at Lohas skin and slimming center on Paseo Saturnino, Banilad. Its a more upscale experience here with your own room, as opposed to being in one large room with dividers, in case privacy is an issue for you. All of their machines and products are brought in from Korea and their staff, like my therapist Jennylyn, are highly knowledgeable and know just how much pressure to apply during the treatment. The service, facilities and products used add up to a luxurious treatment session that makes one feel very pampered.

Published in the Sun.Star Cebu newspaper on August 15, 2014.

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Trying out a stem cell facial

Aug 13, 2014 Growing stem cells in conditions free of animal material makes them safe for use in humans. Credit: Eraxion/iStock/Thinkstock

Human stem cells produced through genetic reprogramming are beset by safety concerns because current techniques alter the DNA of the stem cells and use material from animals to grow them. Now, A*STAR researchers have developed an efficient approach that produces safe, patient-specific human stem cells.

Human induced pluripotent stem cells have the potential to treat a number of diseases without the ethical issues associated with embryonic stem cells. Pluripotent stem cells can be produced from adult cells by introducing genes that reprogram them. Typically, the stem cells are grown on a layer of mouse cells in solutions (known as media) that contain animal proteinsand therefore, potentially may also carry disease. For such stem cells to be safe for use in humans, they need to be grown in 'xeno-free' conditions, which are devoid of material from other animals.

Andrew Wan and Hong Fang Lu at the A*STAR Institute of Bioengineering and Nanotechnology in Singapore and colleagues set out to develop a new xeno-free system. The researchers carried out the genetic reprogramming of cells on an artificially produced protein substrate rather than mouse cells. They also used media that contained no animal components. The result was more efficient reprogramming than seen with conventional approaches.

"A xeno-free system will eliminate the risk of disease transmission from other species, which is important for regulatory approval," explains Wan. "Yet there have been few studies on cell reprogramming under totally xeno-free conditions."

The researchers went one step further by addressing the problem of cells acquiring alterations to their DNA during reprogramming.

"Incorporation of transgenes into the genome of the cell poses another safety issue, risking unwanted genetic alterations," explains Lu. "In our work, the transgenes were introduced to initiate the reprogramming, but after this they were removed from the cell, leading to transgene-free stem cells."

The researchers demonstrated that after genetic reprogramming and the removal of the added genes, the stem cells could still develop into different cells types. They were even able to induce them to form dopaminergic neurons, the type that degenerates in Parkinson's disease. The conditions in which the stem cells were grown mean that they are suitable for clinical use and can be derived from a patient's own cells, ensuring complete compatibility.

"Regulatory approval for clinical application of stem cells largely depends on the conditions in which the stem cells are derived," says Wan. "We present a workable protocol for the reprogramming of fibroblasts to stem cells that minimizes any potential safety risks."

Explore further: Discovery may make it easier to develop life-saving stem cells

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Animal-free reprogramming of adult cells improves safety

HOT SPRINGS | A new proposal to not only save but also enhance the Veterans Affairs hospital in Hot Springs surfaced Monday, and would add not only a medical college but also a medical research component involving the use of stem cells to the facility.

The idea, put forward by an Iowa-based, non-profit corporation, would also be built around treating patients with regenerative therapy, which helps skin grow back.

Bob Krause, president of Veterans National Recover Center, was joined by surgeon Don Swift in Hot Springs to presented the proposal at a press conference Monday morning. Their multi-pronged plan has been submitted for consideration to the VA Black Hills Health Care Systems Environmental Impact Statement.

Our proposal has three main areas, Krause told the small audience that attended the press conference. First, the creation of Battle Mountain College, for the training of doctors in the discipline of osteopathic medicine. Krause noted that by having the additional training, a major first hurdle in the BHHCS proposal to close the Hot Springsan inability to draw doctors to the area would be addressed.

We would also build the Battle Mountain Research Institute, for further research into the regenerative therapies, along with the Battle Mountain Clinic to treat those veterans and others who require this cutting-edge treatment, Krause said.

He added that the proposal stipulated that it is to be considered in its entirety and that if the VA medical center should close, everything is off the table. This proposal is not mutually exclusive of the one presented by Save the VA, he said of the Hot Springs-area group that is fighting to save the hospital from closure by the federal government.

Krause and Swift said that the technology, which was created in Switzerland by the military and is awaiting FDA approval in the United States, utilizes regenerative or restorative cells created from fetal stem cells to jump-start a patients ability to regenerate skin tissue. After the patients own skin begins to grow, the regenerative cells die, Krause said.

He said that submitting the new proposal through the EIS process was important, since the research would need to be conducted on federal property because South Dakota law does not allow stem cell research at this time.

Swift noted that an important part to the regenerative therapy process was access to mineral water to help hydrate the tissue and fight infection. Such water can be found in Hot Springs.

In response to a question, Krause said that he understands that there is a question involving fetal stem cell research. But what is the greater good? he asked. Do we overlook a veteran who has experienced having all of his skin burned away by an [explosion], instead of developing that single cell that could help? Are you going to walk away from that cell?

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New idea for VA would bring an educational focus

17 hours ago The red swamp crayfish (Procambarus clarkii) is native to the southeastern United States. This species is a popular model organism for studies of the nervous system, and has been used to study fundamental mechanisms involved in the production of new neurons in the adult brain. Credit: Jeanne Benton

Researchers have strived for years to determine how neurons are produced and integrated into the brain throughout adult life. In an intriguing twist, scientists reporting in the August 11 issue of the Cell Press journal Developmental Cell provide evidence that adult-born neurons are derived from a special type of circulating blood cell produced by the immune system. The findingswhich were made in crayfishsuggest that the immune system may contribute to the development of the unknown role of certain brain diseases in the development of brain and other tissues.

In many adult organisms, including humans, neurons in some parts of the brain are continually replenished. While this process is critical for ongoing health, dysfunctions in the production of new neurons may also contribute to several neurological diseases, including clinical depression and some neurodegenerative disorders. Dr. Barbara Beltz of Wellesley College and her colleagues studied crayfish to understand how new neurons are made in adult organisms. When they marked the cells of one crayfish and used this animal as a blood donor for transfusions into another crayfish, the researchers found that the donor blood cells could generate neurons in the recipient.

"These blood cellscalled hemocyteshave functions similar to certain white blood cells in mammals and are produced by the immune system in a blood-forming organ that is functionally analogous to bone marrow," explains Dr. Beltz. "When these cells are released into the circulation, they are attracted to a specialized region in the brain where stem cells divide, and their descendants develop into functional neurons."

The current work demonstrates that the immune system can produce cells with stem cell properties that can give rise to different types of cells, including both hemocytes and nerve cells. "Our findings in crayfish indicate that the immune system is intimately tied to mechanisms of adult neurogenesis, suggesting a much closer relationship between the immune system and nervous system than has been previously appreciated," says co-author Dr. Irene Sderhll, of Uppsala University in Sweden. The flexibility of these immune cells in producing neurons in adult animals raises the intriguing possibility of the presence of similar types of flexibility in other animals. If further studies demonstrated a similar relationship between the immune system and brain in mammals, the findings would stimulate a new area of research into immune therapies to target neurological diseases.

Explore further: New discovery on early immune system development

More information: Developmental Cell, Benton et al.: "Cells from the immune system generate adult-born neurons in crayfish." http://www.cell.com/developmental-cel 1534-5807(14)00405-5

Journal reference: Developmental Cell

Provided by Cell Press

Researchers at Lund University have shed light on how and when the immune system is formed, raising hope of better understanding various diseases in children, such as leukaemia.

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Blood cells are new, unexpected source of neurons in crayfish

By Amy Norton HealthDay Reporter

THURSDAY, Aug. 7, 2014 (HealthDay News) -- In a step toward using stem cells to treat paralysis, scientists were able to use cells from an elderly man's skin to regrow nerve connections in rats with damaged spinal cords.

Reporting in the Aug. 7 online issue of Neuron, researchers say the human stem cells triggered the growth of numerous axons -- the fibers that extend from the body of a neuron (nerve cell) to send electrical impulses to other cells.

Some axons even reached the animals' brains, according to the team led by Dr. Mark Tuszynski, a professor of neurosciences at the University of California, San Diego.

"This degree of growth in axons has not been appreciated before," Tuszynski said. But he cautioned that there is still much to be learned about how the new nerve fibers behave in laboratory animals.

Tuszynski likened the potential for stem-cell-induced axon growth to nuclear fusion. If it's contained, you get energy; if it's not contained, you get an explosion.

"Too much axon growth into the wrong places would be a bad thing," Tuszynski said.

For years, researchers have studied the potential for stem cells to restore functioning nerve connections in people with spinal cord injuries. Stem cells are primitive cells that have the capacity to develop into various types of body tissue. Stem cells can come from embryos or be generated from cells taken from a person.

For their study, Tuszynski's team used so-called induced pluripotent stem cells. They took skin cells from a healthy 86-year-old man and genetically reprogrammed them to become similar to embryonic stem cells.

Those stem cells were then used to create primitive neurons, which the researchers embedded into a special scaffold created with the help of proteins called growth factors. From there, the human neurons were grafted into lab rats with spinal cord injuries.

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Scientists Inch Closer Toward Using Stem Cells for Spinal Injuries

For the first time, scientists have uncovered new information on how stem cells in the human bowel behave, revealing vital clues about the earliest stages in bowel cancer development and how we may begin to prevent it.

The study, led by Queen May University of London (QMUL) and published today in the journal Cell Reports, discovered how many stem cells exist within the human bowel and how they behave and evolve over time. It was revealed that within a healthy bowel, stem cells are in constant competition with each other for survival and only a certain number of stem cells can exist within one area at a time (referred to as the 'stem cell niche'). However, when investigating stem cells in early tumours, the researchers saw increased numbers of stem cells within each area as well as intensified competition for survival, suggesting a link between stem cell activity and bowel cancer development.

The study involved studying stem cells directly within the human body using a specially developed 'toolkit'. The toolkit worked by measuring random mutations that naturally accrue in aging stem cells. The random mutations recorded how the stem cells had behaved, similarly to how the rings on a tree trunk record how a tree grew over time. The techniques used were unique in that scientists were able to study the human stem cells within their natural environment, giving a much more accurate picture of their behaviour.

Until this research, the stem cell biology of the human bowel has remained largely a mystery. This is because most stem cell research is carried out in mice, and it was uncertain how research findings in mice could be applied to humans. However, the scientists in fact found the stem cell biology of human bowels to have significant similarities to mice bowels. This means researchers can continue investigating stem cell activity within mice with the knowledge it is representative of humans -- hopefully speeding up bowel cancer research.

Importantly, these new research methods can also now be applied to investigate stem cells in other parts of the human body such as skin, prostate, lung and breast, with the aim of accelerating cancer research in these areas too.

Dr Trevor Graham, Lecturer in Tumour Biology and Study Author at Queen Mary University of London, comments: "Unearthing how stem cells behave within the human bowel is a big step forward for stem cell research. Until now, stem cell research was mostly conducted in mice or involved taking the stem cells out of their natural environment, thus distorting their usual behaviour. We now want to use the methods developed in this study to understand how stem cells behave inside bowel cancer, so we can increase our understanding of how bowel cancer grows. This will hopefully shed more light on how we can prevent bowel cancer -- the fourth most common cancer in the UK. We are positive this research lays important foundations for future bowel cancer prevention work, as well as prevention work in other cancers."

Dr Marnix Jansen, Histopathologist and Study Author at Queen Mary University of London, comments: "This study was made possible through the involvement of patients either diagnosed with bowel cancer or born with a tendency to develop bowel cancer. Only by investigating tissues taken directly from patients could we study how bowel cancers develop. Our work underlines the importance of patient involvement in scientific research if we are to tackle bowel cancer and help the greatest number of people."

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The above story is based on materials provided by Queen Mary, University of London. Note: Materials may be edited for content and length.

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Stem cell behavior of human bowel discovered for first time

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7-Aug-2014

Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press

While neurons normally fail to regenerate after spinal cord injuries, neurons formed from human induced pluripotent stem cells (iPSCs) that were grafted into rats with such injuries displayed remarkable growth throughout the length of the animals' central nervous system. What's more, the iPSCs were derived from skin cells taken from an 86-year-old man. The results, described in the Cell Press journal Neuron, could open up new possibilities in stimulating neuron growth in humans with spinal cord injuries

"These findings indicate that intrinsic neuronal mechanisms readily overcome the barriers created by a spinal cord injury to extend many axons over very long distances and that these capabilities persist even in neurons reprogrammed from very aged human cells," said senior author Mark Tuszynski, MD, PhD, professor of neurosciences and director of the UC San Diego Center for Neural Repair.

After Dr. Tuszynski and his colleagues converted the skin cells into iPSCs, which can be coaxed to develop into nearly any other cell type, the team reprogrammed the cells to become neurons, embedded them in a matrix containing growth factors, and then grafted them into 2-week-old spinal cord injuries in rats.

Three months later, the team found mature neurons and extensive nerve fiber growth across long distances in the rats' spinal cords, including through the wound tissue and even extending into the brain. Despite numerous connections between the implanted neurons and existing rat neurons, functional recovery of the animals' limbs was not restored. The investigators noted that several iPSC grafts contained scars that may have blocked beneficial effects.

Dr. Tuszynski, along with lead author Paul Lu, PhD, of the UC San Diego Department of Neurosciences, and their collaborators are now working to identify the best way to translate neural stem cell therapies for patients with spinal cord injuries, using grafts derived from the patients' own cells.

###

Neuron, Lu et al.: "Long-Distance Axonal Growth from Human Induced Pluripotent Stem Cells After Spinal Cord Injury."

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Human skin cells reprogrammed as neurons regrow in rats with spinal cord injuries

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7-Aug-2014

Contact: Charli Scouller c.scouller@qmul.ac.uk 020-788-27943 Queen Mary, University of London

For the first time, scientists have uncovered new information on how stem cells in the human bowel behave, revealing vital clues about the earliest stages in bowel cancer development and how we may begin to prevent it.

The study, led by Queen May University of London (QMUL) and published today in the journal Cell Reports, discovered how many stem cells exist within the human bowel and how they behave and evolve over time. It was revealed that within a healthy bowel, stem cells are in constant competition with each other for survival and only a certain number of stem cells can exist within one area at a time (referred to as the 'stem cell niche'). However, when investigating stem cells in early tumours, the researchers saw increased numbers of stem cells within each area as well as intensified competition for survival, suggesting a link between stem cell activity and bowel cancer development.

The study involved studying stem cells directly within the human body using a specially developed 'toolkit'. The toolkit worked by measuring random mutations that naturally accrue in ageing stem cells. The random mutations recorded how the stem cells had behaved, similarly to how the rings on a tree trunk record how a tree grew over time. The techniques used were unique in that scientists were able to study the human stem cells within their natural environment, giving a much more accurate picture of their behaviour.

Until this research, the stem cell biology of the human bowel has remained largely a mystery. This is because most stem cell research is carried out in mice, and it was uncertain how research findings in mice could be applied to humans. However, the scientists in fact found the stem cell biology of human bowels to have significant similarities to mice bowels. This means researchers can continue investigating stem cell activity within mice with the knowledge it is representative of humans - hopefully speeding up bowel cancer research.

Importantly, these new research methods can also now be applied to investigate stem cells in other parts of the human body such as skin, prostate, lung and breast, with the aim of accelerating cancer research in these areas too.

Dr Trevor Graham, Lecturer in Tumour Biology and Study Author at Queen Mary University of London, comments: "Unearthing how stem cells behave within the human bowel is a big step forward for stem cell research. Until now, stem cell research was mostly conducted in mice or involved taking the stem cells out of their natural environment, thus distorting their usual behaviour. We now want to use the methods developed in this study to understand how stem cells behave inside bowel cancer, so we can increase our understanding of how bowel cancer grows. This will hopefully shed more light on how we can prevent bowel cancer the fourth most common cancer in the UK. We are positive this research lays important foundations for future bowel cancer prevention work, as well as prevention work in other cancers."

Dr Marnix Jansen, Histopathologist and Study Author at Queen Mary University of London, comments: "This study was made possible through the involvement of patients either diagnosed with bowel cancer or born with a tendency to develop bowel cancer. Only by investigating tissues taken directly from patients could we study how bowel cancers develop. Our work underlines the importance of patient involvement in scientific research if we are to tackle bowel cancer and help the greatest number of people."

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Scientists uncover stem cell behavior of human bowel for the first time

23 hours ago A bam mutant fruit fly ovary, known as the germanium, contains only adult stem cell-like cells (red) and spherical spectrosome (green). The accumulation of only adult stem cell-like cells indicates a mutation in the master differentiation factor bam completely blocks germline stem cell lineage differentiation. Credit: Ting Xie, Ph.D., Stowers Institute for Medical Research

Adult organisms ranging from fruit flies to humans harbor adult stem cells, some of which renew themselves through cell division while others differentiate into the specialized cells needed to replace worn-out or damaged organs and tissues.

Understanding the molecular mechanisms that control the balance between self-renewal and differentiation in adult stem cells is an important foundation for developing therapies to regenerate diseased, injured or aged tissue.

In the current issue of the journal Nature, scientists at the Stowers Institute for Medical Research report that competition between two proteins, Bam and COP9, balances the self-renewal and differentiation functions of ovarian germline stem cells (GSCs) in fruit flies (Drosophila melanogaster).

"Bam is the master differentiation factor in the Drosophila female GSC system," says Stowers Investigator Ting Xie, Ph.D., and senior author of the Nature paper. "In order to carry out the switch from self-renewal to differentiation, Bam must inactivate the functions of self-renewing factors as well as activate the functions of differentiation factors."

Bam, which is encoded by the gene with the unusual name of bag-of-marbles, is expressed at high levels in differentiating cells and very low levels in GSCs of fruit flies.

Among the self-renewing factors targeted by Bam is the COP9 signalosome (CSN), an evolutionarily conserved, multi-functional complex that contains eight protein sub-units (CSN1 to CSN8). Xie and his collaborators discovered that Bam and the COP9 sub-unit known as CSN4 have opposite functions in regulating the fate of GSCs in female fruit flies.

Bam can switch COP9 function from self-renewal to differentiation by sequestering and antagonizing CSN4, Xie says. "Bam directly binds to CSN4, preventing its association with the seven other COP9 components via protein competition," he adds. CSN4 is the only COP9 sub-unit that can interact with Bam.

"This study has offered a novel way for Bam to carry out the switch from self-renewal to differentiation," says Xie, whose lab uses a combination of genetic, molecular, genomic and cell biological approaches to investigate GSCs as well as somatic stem cells of fruit flies.

In the Nature paper, Xie's lab also reports that CSN4 is the only one of the eight sub-units that is not involved in the regulation of GSC differentiation of female fruit flies. "One possible explanation for the opposite effects of CSN4 and the other CSN proteins is that the sequestration of CSN4 by Bam allows the other CSN proteins to have differentiation-promoting functions," he says.

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Team reveals molecular competition drives adult stem cells to specialize

The Dr Hadwen Trust awarded 135,078 to Dr Catherine Wright, a lecturer at the Department of Life Sciences at Glasgow Caledonian University and a member of the Institute for Applied Health Research's Diabetes and Biomedical Sciences research group.

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The grant will fund a three-year research programme which will allow the university's skin tissue bank to continue providing human skin tissue and cells that can be used for studies related to diabetes research.

This includes issues such as wound healing, as well as the development of human stem cells - which would help to replace the need for animal experimentation.

Dr Wright said: "The funding will allow us to employ a full-time member of staff to assist the academics to run the tissue bank and develop new types of human cell models that can replace animal experiments."

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Diabetes project is given funding boost

Brain cells that were grafted into the brains of mice have become fully functionally integrated after six months. The successful neuron transplant could pave the way for therapies to treat neurodegenerative diseases such as Parkinson's.

A team of stem cell researchers at the Luxembourg Centre for Systems Biomedicine created the grafted neurons -- induced neuronal stem cells -- in a petri dish out of the host's reprogrammed skin cells. This technique dramatically improved the compatibility of the implanted cells.

Six months after the brain cells were implanted into the hippocampus and cortex regions of the brain, the neurons were fully integrated with the original brain cells via newly formed synapses (the contact points between neurons). The induced neuronal stem cells had changed into different types of brain cells -- neurons, astrocytes and oligodendrocytes -- over time within the host brain. Functional integration with the existing network of cells is absolutely critical for long-term survival of the new brain tissue. The new brain cells exhibited normal activity in tests and the mice showed no adverse side effects.

The plan for researchers is now to explore replacing the type of neurons that tend to die off in the brain of Parkinson's patients -- those neurons found in the substantia nigra that produce dopamine. It may, in the future, be possible to implant neurons to produce the diminished dopamine, which could prove to be an effective treatment for the disease.

Of course, it's a bit leap from the current research to human trials. "Successes in human therapy are still a long way off, but I am sure successful cell replacement therapies will exist in future," says team leader and stem cell researcher Jens Schwamborn. "Our research results have taken us a step further in this direction."

The study has been published in Stem Cell Reports and is available to read for free.

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Implanted brain cells integrate fully with mouse brain tissue

Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have grafted neurons reprogrammed from skin cells into the brains of mice for the first time with long-term stability. Six months after implantation, the neurons had become fully functionally integrated into the brain. This successful, lastingly stable, implantation of neurons raises hope for future therapies that will replace sick neurons with healthy ones in the brains of Parkinson's disease patients, for example.

The Luxembourg researchers published their results in the current issue of Stem Cell Reports.

The LCSB research group around Prof. Dr. Jens Schwamborn and Kathrin Hemmer is working continuously to bring cell replacement therapy to maturity as a treatment for neurodegenerative diseases. Sick and dead neurons in the brain can be replaced with new cells. This could one day cure disorders such as Parkinson's disease. The path towards successful therapy in humans, however, is long. "Successes in human therapy are still a long way off, but I am sure successful cell replacement therapies will exist in future. Our research results have taken us a step further in this direction," declares stem cell researcher Prof. Schwamborn, who heads a group of 15 scientists at LCSB.

In their latest tests, the research group and colleagues from the Max Planck Institute and the University Hospital Mnster and the University of Bielefeld succeeded in creating stable nerve tissue in the brain from neurons that had been reprogrammed from skin cells. The stem cell researchers' technique of producing neurons, or more specifically induced neuronal stem cells (iNSC), in a petri dish from the host's own skin cells considerably improves the compatibility of the implanted cells. The treated mice showed no adverse side effects even six months after implantation into the hippocampus and cortex regions of the brain. In fact it was quite the opposite -- the implanted neurons were fully integrated into the complex network of the brain. The neurons exhibited normal activity and were connected to the original brain cells via newly formed synapses, the contact points between nerve cells.

The tests demonstrate that the scientists are continually gaining a better understanding of how to treat such cells in order to successfully replace damaged or dead tissue. "Building upon the current insights, we will now be looking specifically at the type of neurons that die off in the brain of Parkinson's patients -- namely the dopamine-producing neurons," Schwamborn reports. In future, implanted neurons could produce the lacking dopamine directly in the patient's brain and transport it to the appropriate sites. This could result in an actual cure, as has so far been impossible. The first trials in mice are in progress at the LCSB laboratories on the university campus Belval.

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The above story is based on materials provided by Universit du Luxembourg. Note: Materials may be edited for content and length.

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Implanted neurons become part of the brain, mouse study shows

04.08.2014 - (idw) Universitt Luxemburg - Universit du Luxembourg

Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have grafted neurons reprogrammed from skin cells into the brains of mice for the first time with long-term stability. Six months after implantation, the neurons had become fully functionally integrated into the brain. This successful, because lastingly stable, implantation of neurons raises hope for future therapies that will replace sick neurons with healthy ones in the brains of Parkinsons disease patients, for example. The Luxembourg researchers published their results in the current issue of Stem Cell Reports. The LCSB research group around Prof. Dr. Jens Schwamborn and Kathrin Hemmer is working continuously to bring cell replacement therapy to maturity as a treatment for neurodegenerative diseases. Sick and dead neurons in the brain can be replaced with new cells. This could one day cure disorders such as Parkinsons disease. The path towards successful therapy in humans, however, is long. Successes in human therapy are still a long way off, but I am sure successful cell replacement therapies will exist in future. Our research results have taken us a step further in this direction, declares stem cell researcher Prof. Schwamborn, who heads a group of 15 scientists at LCSB.

In their latest tests, the research group and colleagues from the Max Planck Institute and the University Hospital Mnster and the University of Bielefeld succeeded in creating stable nerve tissue in the brain from neurons that had been reprogrammed from skin cells.

The tests demonstrate that the scientists are continually gaining a better understanding of how to treat such cells in order to successfully replace damaged or dead tissue. Building upon the current insights, we will now be looking specifically at the type of neurons that die off in the brain of Parkinsons patients namely the dopamine-producing neurons, Schwamborn reports. In future, implanted neurons could produce the lacking dopamine directly in the patients brain and transport it to the appropriate sites. This could result in an actual cure, as has so far been impossible. The first trials in mice are in progress at the LCSB laboratories on the university campus Belval. Weitere Informationen:http://www.cell.com/stem-cell-reports/abstract/S2213-6711%2814%2900203-3 - Link to the scientific paperhttp://www.uni.lu/lcsb - link to the Luxembourg Centre for Systems Biomedicine

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Implanted Neurons become Part of the Brain

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Luxury Skin Care: SkinStore.com Adds Reformulated, Repackaged DermaQuest

A major hurdle in gene therapy is the efficient integration of a corrected gene into a patient's genome without mutating off-target sites. In a paper published today in Genome Research, scientists have used CRISPR/Cas genome editing technology to seamlessly and efficiently correct disease-causing mutations in cells from patients with -thalassemia.

-thalassemia results from inherited DNA mutations in the hemoglobin beta (HBB) gene, resulting in reduced HBB expression in red blood cells and, in the most severe forms, anemia. The only established curative treatment is hematopoietic stem cell transplantation; however, this treatment requires a matched donor. Gene therapy, which delivers a corrected copy of a gene into patient cells, could bypass the need for a donor. Previous attempts using a virus to randomly insert a normal gene into the genome has been successful in one -thalassemia patient, but the long-term effect of viral insertion is not yet known.

To correct HBB mutations directly in a patient's genome, researchers first generated induced pluripotent stem cells, or iPSCs, from skin cells of patients. The real breakthrough came when they applied CRISPR/Cas9 to precisely engineer a double strand DNA break at the HBB locus in these cells, allowing a donor plasmid with the corrected sites to be efficiently integrated, thus replacing the mutated sites. The donor plasmid also contained selectable markers to identify cells with corrected copies of the gene. These selectable markers were subsequently removed with transposase and a second round of selection, generating a seamless, corrected version of HBB in the patient's genome.

Importantly, the researchers could differentiate the corrected iPSCs into mature blood cells, and these blood cells showed restored expression of hemoglobin. However, much work is needed before these cells could be transplanted back into a patient for treating -thalassemia. "Although we and others are able to differentiate iPSCs into blood cell progenitors as well as mature blood cells, the transplantation of the progenitors into mouse models to test them has so far proven very difficult," said senior author Yuet Wai Kan from the University of California, San Francisco. "I believe it will take quite a few more years before we can apply it in a clinical setting."

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Seamless gene correction of beta-thalassemia mutations in patient-specific cells

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Next time you come across an advertisement offering cosmetic stem cell procedures not only to give your skin a glowing look but also to stop it from growing old, beware.

Most of such ads claim benefits from procedures that have not undergone rigorous scientific evaluation - including potential risks related to stem cell and tissue processing and the effects of ageing on stem cells, a new research warns.

"Stem cells offer tremendous potential but the marketplace is saturated with unsubstantiated and sometimes fraudulent claims that may place patients at risk," warned Michael T. Longaker from Stanford University's Medical Center.

The procedures marketed as "stem cell facelifts" are often just "lipofilling" procedures, "an established fat injection technique with no prolonged anti-ageing effect", Longaker added.

To gain insight into these claims, researchers performed a Google search for cosmetic stem cell treatments, the most common of which was "stem cell facelift".

Most procedures used "stem cells" isolated from fat.

However, the websites provided little information on the quality of the stem cells used.

Without advanced cell-sorting procedures, the products used in these procedures likely contain many other types of cells besides fat-derived stem cells.

To date, just one stem cell procedure for cosmetic purpose has received the approval from the US Food and Drugs Administration (FDA).

That product, designed to treat fine facial wrinkles, is undergoing extensive post-approval surveillance.

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'Most stem cell-based cosmetic surgeries fake'