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.

The rest is here:
Stem cell behavior of human bowel discovered for first time

PUBLIC RELEASE DATE:

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

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Newswise Building upon previous research, scientists at the University of California, San Diego School of Medicine and Veterans Affairs San Diego Healthcare System report that neurons derived from human induced pluripotent stem cells (iPSC) and grafted into rats after a spinal cord injury produced cells with tens of thousands of axons extending virtually the entire length of the animals central nervous system.

Writing in the August 7 early online edition of Neuron, lead scientist Paul Lu, PhD, of the UC San Diego Department of Neurosciences and colleagues said the human iPSC-derived axons extended through the white matter of the injury sites, frequently penetrating adjacent gray matter to form synapses with rat neurons. Similarly, rat motor axons pierced the human iPSC grafts to form their own synapses.

The iPSCs used were developed from a healthy 86-year-old human male.

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.

For several years, Tuszynski and colleagues have been steadily chipping away at the notion that a spinal cord injury necessarily results in permanent dysfunction and paralysis. Earlier work has shown that grafted stem cells reprogrammed to become neurons can, in fact, form new, functional circuits across an injury site, with the treated animals experiencing some restored ability to move affected limbs. The new findings underscore the potential of iPSC-based therapy and suggest a host of new studies and questions to be asked, such as whether axons can be guided and how will they develop, function and mature over longer periods of time.

While neural stem cell therapies are already advancing to clinical trials, this research raises cautionary notes about moving to human therapy too quickly, said Tuszynski.

The enormous outgrowth of axons to many regions of the spinal cord and even deeply into the brain raises questions of possible harmful side effects if axons are mistargeted. We also need to learn if the new connections formed by axons are stable over time, and if implanted human neural stem cells are maturing on a human time frame months to years or more rapidly. If maturity is reached on a human time frame, it could take months to years to observe functional benefits or problems in human clinical trials.

In the latest work, Lu, Tuszynski and colleagues converted skin cells from a healthy 86-year-old man into iPSCs, which possess the ability to become almost any kind of cell. The iPSCs were then reprogrammed to become neurons in collaboration with the laboratory of Larry Goldstein, PhD, director of the UC San Diego Sanford Stem Cell Clinical Center. The new human neurons were subsequently embedded in a matrix containing growth factors and grafted into two-week-old spinal cord injuries in rats.

Excerpt from:
Dramatic Growth of Grafted Stem Cells in Rat Spinal Cord Injuries

PUBLIC RELEASE DATE:

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.

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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