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  • richardmitnick 9:49 am on March 17, 2016 Permalink | Reply
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    From phys.org: “Scientists generate a new type of human stem cell that has half a genome” 

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    phys.org

    March 16, 2016
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    Scientists from The Hebrew University of Jerusalem, Columbia University Medical Center (CUMC) and The New York Stem Cell Foundation Research Institute (NYSCF) have succeeded in generating a new type of embryonic stem cell that carries a single copy of the human genome, instead of the two copies typically found in normal stem cells. The scientists reported their findings today in the journal Nature.

    1
    A haploid cell with 23 chromosomes (left), and a diploid cell with 46 chromosomes (right). Credit: Columbia University Medical Center/Hebrew University

    The stem cells described in this paper are the first human cells that are known to be capable of cell division with just one copy of the parent cell’s genome.

    Human cells are considered ‘diploid’ because they inherit two sets of chromosomes, 46 in total, 23 from the mother and 23 from the father. The only exceptions are reproductive (egg and sperm) cells, known as ‘haploid’ cells because they contain a single set of 23 chromosomes. These haploid cells cannot divide to make more eggs and sperm.

    Previous efforts to generate embryonic stem cells using human egg cells had resulted in diploid stem cells. In this study, the scientists triggered unfertilized human egg cells into dividing. They then highlighted the DNA with a fluorescent dye and isolated the haploid stem cells, which were scattered among the more populous diploid cells.

    The researchers showed that these haploid stem cells were pluripotent—meaning they were able to differentiate into many other cell types, including nerve, heart, and pancreatic cells—while retaining a single set of chromosomes.

    “This study has given us a new type of human stem cell that will have an important impact on human genetic and medical research,” said Nissim Benvenisty, MD, PhD, Director of the Azrieli Center for Stem Cells and Genetic Research at the Hebrew University of Jerusalem and principal co-author of the study. “These cells will provide researchers with a novel tool for improving our understanding of human development, and the reasons why we reproduce sexually, instead of from a single parent.”

    The researchers were also able to show that by virtue of having just a single copy of a gene to target, haploid human cells may constitute a powerful tool for genetic screens. Being able to affect single-copy genes in haploid human stem cells has the potential to facilitate genetic analysis in biomedical fields such as cancer research, precision and regenerative medicine.

    “One of the greatest advantages of using haploid human cells is that it is much easier to edit their genes,” explained Ido Sagi, the PhD student who led the research at the Azrieli Center for Stem Cells and Genetic Research at the Hebrew University of Jerusalem. In diploid cells, detecting the biological effects of a single-copy mutation is difficult, because the other copy is normal and serves as “backup.”

    Since the stem cells described in this study were a genetic match to the egg cell donor, they could also be used to develop cell-based therapies for diseases such as blindness, diabetes, or other conditions in which genetically identical cells offer a therapeutic advantage. Because their genetic content is equivalent to germ cells, they might also be useful for reproductive purposes.

    “This work is an outstanding example of how collaborations between different institutions, on different continents, can solve fundamental problems in biomedicine,” said Dieter Egli, PhD, principal co-author of the study, and Assistant Professor of Developmental Cell Biology in Pediatrics at Columbia University Medical Center and a Senior Research Fellow at the NYSCF Research Institute and a NYSCF-Robertson Investigator.

    The research, supported by The New York Stem Cell Foundation, the New York State Stem Cell Science Program, and by the Azrieli Foundation, underscores the importance of private philanthropy in advancing cutting-edge science.

    More information: Ido Sagi et al. Derivation and differentiation of haploid human embryonic stem cells, Nature (2016). DOI: 10.1038/nature17408

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  • richardmitnick 8:17 pm on March 15, 2016 Permalink | Reply
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    From CSIRO: “The not-so-big BOP revolutionising stem cell harvesting” 

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    Commonwealth Scientific and Industrial Research Organisation

    16th March 2016
    Ali Green

    Did you know the human body needs to produce one million blood cells every second of every day to live? In patients with leukaemia, rapidly multiplying abnormal white blood cells outcompete healthy cells, leaving the body starved of oxygen and lacking immunity.

    Treatment for this disease includes chemotherapy that kill the leukaemia cells, but as a consequence, the healthy bone marrow cells are also destroyed. To replenish the bone marrow cells a stem cell transplant is given. But up until recently the process for harvesting stem cells for leukaemia treatment was a super invasive procedure that entailed an injection into the hip or spine to extract the stem cell rich marrow. Thankfully, these days stem cells can be harvested much less invasively through peripheral blood stem-cell transplants (PBSCTs), as an out-patient procedure.

    In a PBSCT, a donor’s stem cells are taken from their bloodstream and separated from their other blood components in a process called apheresis. The blood is then returned to the donor and the harvested stem cells frozen for later use. When a patient is ready, the stem cells are transplanted into their bloodstream intravenously.

    A hematopoietic stem cell (HSC) being mobilised from the bone marrow microenvironment into a blood vessel. Credit Dr Kate Patterson (Garvan Institute of Medical Research, NSW)
    A hematopoietic stem cell (HSC) being mobilised from the bone marrow microenvironment into a blood vessel. Credit Dr Kate Patterson (Garvan Institute of Medical Research, NSW)

    Normally, stem cells in the bloodstream are very rare and are insufficient in number to give a successful transplant. To stimulate the release of stem cells from the bone marrow, donors are injected with multiple doses of a substance known as a ‘growth factor’ (G-CSF). The injections, which are given in the stomach, leg or arm in the days leading up to the harvesting procedure, stimulate production of stem cells to the point that they can spill over from the marrow and into the blood, where they can be easily collected. This process is called stem cell mobilisation.

    G-CSF takes up to a week to take effect and in some cases, donors don’t respond well to the growth factor – that is, their stem cell count doesn’t get high enough for a successful transplant. To get around this, these ‘poor mobilisers’ are also given a dose of AMD3100 – a molecule that, when combined with the growth factor, can increase the number of stem cells in the blood, and therefore harvesting success rate.

    What AMD3100 can’t improve however, are the nasty side effects, like bone pain and spleen enlargement, that the growth factor can cause for some donors. Unfortunately, AMD3100 is not capable of mobilising enough stem cells when used alone for clinical transplant purposes.

    In light of this, our scientists were driven to find an alternative approach to stem cell harvesting that could eliminate the use of the growth factor. The team, led by Associate Professor Susie Nilsson, knew that the bone marrow stem cells that have the most potent activity like to anchor near the bone/bone marrow interface, or the endosteal region, and that one of their key characteristics is their ability to remain in a dormant state.

    There are proteins that help them do this. Called ECMs, or extracellular matrix, this collection of molecules play an important role in keeping stem cells in the right area and help to regulate their maintenance and function. Working out how to target these proteins to mobilise the stem cells could eliminate the need for growth factor, and get around the problem of side effects.

    So our team, together with the Australian Regenerative Medicine Institute (ARMI) at Monash, set about developing a molecule to do just this.

    They discovered that if they combined their small molecule, N-(benzenesulfonyl)-L-proly1-L-0-(1 pyrrolidinycarbony1)tyrosine, or BOP for short, with AMD3100, they could adequately mobilise the stem cells without the need of growth factor. They also show that the molecule BOP specifically targets the potent endosteal stem cells in the bone marrow.

    It was found that a single dose of small molecule BOP, combined with AMD3100, could directly impact stem cells – and fast. Stem cells could be seen in the blood just one hour after dosage and when transplanted could replenish the entire bone marrow system. As well as causing no known side effects, the benefit of this discovery is that harvesting stem cells becomes even less invasive for patients who are already under considerable stress. Small molecule injections provide a ‘one stop’ deal where patients can come and go in the space of an hour for a stem cell harvesting procedure that used to take days.

    So far successful pre-clinical studies in mouse and human-mouse models have demonstrated the effectiveness of BOP. The next step is a phase 1 clinical trial assessing the combination of BOP molecule with growth factor, and phase 2, the successful combination of the two small molecules BOP and AMD3100.

    See the full article here .

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  • richardmitnick 4:48 pm on February 5, 2016 Permalink | Reply
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    From Rochester: “Scientists Discover Stem Cells Capable of Repairing Skull, Face Bones” 

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    University of Rochester

    February 01, 2016
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    A team of Rochester scientists has, for the first time, identified and isolated a stem cell population capable of skull formation and craniofacial bone repair in mice—achieving an important step toward using stem cells for bone reconstruction of the face and head in the future, according to a new paper in Nature Communications.

    stem cells
    The photo shows a blue-stained stem cell and a red-stained stem cell that each generated new bones cells after transplantation

    Senior author Wei Hsu, Ph.D., dean’s professor of Biomedical Genetics and a scientist at the Eastman Institute for Oral Health at theUniversity of Rochester Medical Center, said the goal is to better understand and find stem-cell therapy for a condition known as craniosynostosis, a skull deformity in infants. Craniosynostosis often leads to developmental delays and life-threatening elevated pressure in the brain.

    Hsu believes his findings contribute to an emerging field involving tissue engineering that uses stem cells and other materials to invent superior ways to replace damaged craniofacial bones in humans due to congenital disease, trauma, or cancer surgery.

    For years Hsu’s lab, including the study’s lead author, Takamitsu Maruyama, Ph.D., focused on the function of the Axin2 gene and a mutation that causes craniosynostosis in mice. Because of a unique expression pattern of the Axin2 gene in the skull, the lab then began investigating the activity of Axin2-expressing cells and their role in bone formation, repair and regeneration. Their latest evidence shows that stem cells central to skull formation are contained within Axin2 cell populations, comprising about 1 percent—and that the lab tests used to uncover the skeletal stem cells might also be useful to find bone diseases caused by stem cell abnormalities.

    The team also confirmed that this population of stem cells is unique to bones of the head, and that separate and distinct stem cells are responsible for formation of long bones in the legs and other parts of the body, for example.

    The National Institutes of Health and NYSTEM funded the research.

    See the full article here .

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    The University of Rochester is one of the country’s top-tier research universities. Our 158 buildings house more than 200 academic majors, more than 2,000 faculty and instructional staff, and some 10,500 students—approximately half of whom are women.

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  • richardmitnick 4:32 pm on January 8, 2016 Permalink | Reply
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    From Broad Institute: “Stem cells push back the frontiers of psychiatric research” 

    Broad Institute

    Broad Institute

    January 6th, 2016
    Leah Eisenstadt

    Temp 1
    Members of the Stanley Center’s Stem Cell Program use pluripotent stem cells to generate human neurons (in green) for exploring the genetics of mental illness. Image courtesy of Lindy Barrett.

    The human brain is notoriously difficult to study. The organ is home to billions of cells that come in hundreds of flavors, woven into a network of trillions of dynamic cellular connections that make it one of the most complex structures in the body. It is the seat of decidedly human traits like language, creativity, and higher cognition that set us apart from other organisms, making animal models less than ideal for studying human illnesses like psychiatric disease.

    In addition, the brain is ethically and practically inviolable. Unlike studies of cancer or immune disorders, in which diseased tissue can be sampled relatively easily, obtaining neurons from living people is unfeasible. Research volunteers are unlikely to consent to the biopsy of their brain tissue and even if they did, growing them in a dish would be no easy task.

    The ideal experimental model for studying psychiatric disease would be an easily replenished supply of human brain cells – for example, by generating them from so-called “pluripotent” stem cells that can theoretically be coaxed into neurons or other brain cell types – but until very recently, such a crucial research tool didn’t exist.

    In recent years, scientists have turned to the human genome for insight on the genes and biological processes that underlie mental illness, in hopes of shedding light on the brain’s inner workings in health and disease and charting new therapeutic and diagnostic avenues. Over the past decade, researchers at the Stanley Center for Psychiatric Research at the Broad Institute have helped assemble large international collections of DNA from people with and without psychiatric disease and performed large-scale analyses to identify genetic risk factors. These efforts have been hugely successful; for example, more than 100 genetic regions have been linked to schizophrenia, and many more are likely to come.

    But this success has also painted a daunting picture of the complexity associated with the genetics of psychiatric disorders. Many of these illnesses are “polygenic,” meaning they are influenced by the cumulative, subtle effects of a great number of genetic variations, rather than caused by a single mutation of large effect. To make sense of the many genetic risk factors coming out of human genomic studies, scientists need new, high-throughput ways to study how those genetic variations impact the function of brain cells.

    Recognizing that unique approaches are needed to make headway in mental illness, a growing team of scientists in the Stanley Center’s Stem Cell Program aims to build an innovative resource for cellular studies of neurobiology and psychiatric disease: a “biobank” of hundreds of stem cell lines that will enable the analysis of these disorders at a resolution and scale unheard of in neuroscience.

    Led by Kevin Eggan, an institute member of the Broad and a professor in the Department of Stem Cell and Regenerative Biology at Harvard University, the group harnesses the latest advances in stem cell science, cellular reprogramming, and gene-editing technology to generate functioning human neurons in the dish. These cellular models will be crucial to unraveling the biological roots of psychiatric diseases, to charting new therapeutic avenues, and to shedding light on normal brain physiology and development.

    “One of the great challenges in studying psychiatric diseases is that they’re so polygenic. Our understanding of the genetics underlying these disorders is growing, yet it’s still far behind other diseases like cancer,” said Lindy Barrett, a group leader in the Stem Cell Program. “To understand what’s going wrong in the brain, we need large collections of cell lines with diverse genetic makeup to cover all the genome variation in disease.”

    To create this new biobank, Eggan, Barrett, and their colleagues turned to “pluripotent” stem cells, which have the capacity to become many different cell types in the body. With the right coaxing in the lab, pluripotent cells could spawn a nearly endless supply of human brain cells for research.

    Since the Stem Cell Program’s founding in 2014, the researchers have been building infrastructure in their lab spaces at both the Broad’s Stanley Center and at Harvard University, and refining protocols to generate neurons from pluripotent stem cells.

    The process begins with fibroblasts – most often, from skin biopsies – taken from healthy volunteers or from patients with psychiatric diseases that are collected at partner institutions such as McLean Hospital. Those fibroblasts are then sent to collaborators at the New York Stem Cell Foundation, where they spend several months being “reprogrammed” into less specialized cells, known as induced pluripotent stem (iPS) cells. The iPS cells are sent to the group’s labs at Harvard and Broad, where they can be treated with a particular cocktail of factors to “differentiate,” or mature, into neuronal cells.

    In addition to studying the effects of natural genetic variation in patient populations, the researchers want the ability to engineer precise genetic variants in neurons, an incredibly useful tool for investigating the role of genes and variants identified in large-scale genomic studies. To do so, they harness the power of the cutting-edge gene-editing technology known as CRISPR-Cas9. Using this genetic “cut-and-paste” method, they can introduce single or multiple genetic changes into iPS cells or embryonic stem cells (pluripotent cells isolated from human embryos, rather than derived from specialized cells like fibroblasts) and isolate the effects of just those changes in the resulting differentiated neurons.

    With these custom-made cell lines, scientists within the Stanley Center and beyond can investigate the functional effects of particular patterns of genetic variation in a high-throughput manner, using a variety of experimental assays in the lab. “For the Stanley Center, this is the first real opportunity to approach cellular studies with such statistical power,” said Eggan. “We can investigate the underlying cell biology of these polygenic illnesses at a larger scale than what’s been done before, and with genetic diversity that more accurately reflects what we see in the population.”

    For now, the team is focused on generating excitatory cortical neurons because of evidence for changes in the cortex (the brain’s outer layer, responsible for many facets of cognitive function) in psychiatric disease. The researchers hope to eventually generate other brain cell types, including astrocytes and interneurons, to explore the involvement of the brain’s many cell types in disease and the effects of disease-linked variants on those cells. So far, they’ve been able to reliably produce neurons that resemble brain cells at an early stage of maturation, which are useful for studying disorders of early neurodevelopment. They are also working with the Broad’s Center for the Development of Therapeutics to explore options for automating some steps of the differentiation process, to allow them to scale up even further.

    The Stem Cell Program plans to bank human cell lines that can be shared with others to conduct original research. “We want to share these tools and empower other researchers so they can make discoveries about the molecules and pathways involved in psychiatric disease and, hopefully, one day identify new treatments for these illnesses based on the underlying biology,” said Barrett.

    See the full article here .

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  • richardmitnick 12:29 pm on December 27, 2015 Permalink | Reply
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    From Wyss: “Changing the fate of stem cells” 

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    Nov 30, 2015 [This was just put up]
    Leah Burrows

    Temp 1
    These scanning electron microscopy images show a cross section of the novel fast-relaxing hydrogel developed by David Mooney and his team at the Wyss Institute and SEAS. The hydrogels mimic natural tissues properties and trigger stem cells to differentiate into osteoblasts (bone-forming cells). Credit: Wyss Institute at Harvard University/Harvard SEAS

    Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a new, more precise way to synthetically control differentiation of stem cells into bone cells by leveraging bioinspired hydrogels. This new technique has promising applications in the realm of bone regeneration, growth and healing. The research led by David Mooney, Ph.D., Wyss Institute Core Faculty member and Robert P. Pinkas Family Professor of Bioengineering at SEAS, was published on November 30 in Nature Materials.

    The extracellular matrix, a microenvironment of proteins and polymers that surrounds and connects cells, impacts a range of cellular behaviors including differentiation. For about a decade, researchers have been able to direct the fate of stem cells by tuning the mechanical stiffness of synthetic microenvironments such as hydrogels. Stem cells in more flexible hydrogels have been shown to differentiate into fat cells while those in stiffer hydrogels are more likely to differentiate into osteogenic (bone) cells.

    But tuning stiffness alone is not precise enough to overcome many of the challenges in differentiating and proliferating different types of stem cells. Only tuning the stiffness of a cell’s microenvironment assumes that the natural extracellular matrix behaves elastically like rubber. When force or stress is exerted on an elastic material, it is stored as energy, and when that force is removed the material bounces back to its original shape like a rubber band. In nature, however, extracellular matrices are not elastic — they are viscoelastic. Viscoelastic materials, such as chewing gum or Silly Putty, relax over time when force or stress is applied.

    “This work both provides new insight into the biology of regeneration, and is allowing us to design materials that actively promote tissue regeneration,” said Mooney.

    Mooney and his team decided to mimic the viscoelasticity of living tissue by developing a novel hydrogel containing tunable stress relaxation responses. When they put stem cells into this viscoelastic microenvironment and tuned the speed at which the gel relaxed, they observed dramatic changes in the behavior and differentiation of the cells.

    Temp 2
    In this scanning electron microscopy image, stem cells can be seen cultured on the novel fast-relaxing hydrogel. The properties of the hydrogel will direct the stem cells to differentiate into bone cells. The new hydrogel could potentially have important biomedical applications in bone regeneration, growth and healing. Credit: Wyss Institute at Harvard University/Harvard SEAS

    “We found that by increasing stress relaxation, especially combined with increased stiffness in the hydrogel, there is an increase of osteogenic differentiation,” said Luo Gu, Postdoctoral Fellow at SEAS and Wyss and co-first author on the paper. “With increased stress relaxation, there was also a decreases the differentiation of fat cells. This is the first time we’ve observed how stress relaxation impacts cell differentiation.”

    Not only did increased stress relaxation dramatically increase early osteogenic differentiation but those cells continued to develop toward full–fledged bone cells.

    One reason that fast–relaxing microenvironments promote more osteogenesis and form bone is that cells inside these matrices can mechanically remodel the matrix and more easily change shape, said Ovijit Chaudhuri, a former Postdoctoral Fellow at SEAS and Wyss and co–first author on the study. It may seem counterintuitive that bone cells need fast–relaxing environments to grow into fully–formed strong, stiff bones. However, the team observed that the natural microenvironment around bone fractures is very similar to the fastest–relaxing hydrogel the team developed in the lab.

    “Coagulated bone marrow and blood near a fracture are very viscous,” Gu said. “This is a good indication that in the natural environment, when a bone fracture is healing, it needs a really fast–relaxing matrix to assist in bone growth.”

    Although no single microenvironment parameter alone controls differentiation, Gu said, combined tuning of hydrogel stress relaxation responses with stiffness properties provides a new way to more precisely control stem cell differentiation and development. The next stage of the research is to test fast-relaxing hydrogels in vivo, to see if they promote bone healing.

    The work was funded by the National Institute of Health, the Einstein Foundation Berlin and Harvard MRSEC.

    See the full article here .

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    The Wyss (pronounced “Veese”) Institute for Biologically Inspired Engineering uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world.

    Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs.

     
  • richardmitnick 2:44 pm on December 25, 2015 Permalink | Reply
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    From Stanford: “One (blood stem) cell to rule them all? Perhaps not, say Stanford researchers” 

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    Stanford University

    December 24th, 2015
    Krista Conger

    1
    Photo by Alden Chadwick

    The blood stem cell, or hematopoietic stem cell, is a cell that’s believed to give rise to all the components of the blood and immune system. Nestled in our bone marrow, it springs into action as necessary and is a key component of bone marrow transplantation procedures (more accurately called hematopoietic stem cell transplantation) conducted to save patients with blood diseases or whose immune systems have been wiped out by large doses of chemotherapy or radiation.

    But new research published today in Stem Cell Reports by research associate Eliver Ghosn, PhD, and colleagues in the laboratory of geneticist Leonore Herzenberg suggests that, at least in laboratory mice, this stem cell may not be as omnipotent as previously thought. In particular, it seems unable to give rise to an important subpopulation of B cells, a type of immune cell. As Ghosn explained to me in an email:

    “Briefly, our findings challenge the idea that a single blood, or hematopoietic, stem cell (HSC) can fully regenerate all components of the immune system. We’ve shown that transplantation with highly purified HSCs fails to fully regenerate the B lymphocyte compartment, which is needed to protect against infections such as influenza, pneumonia and other infectious diseases, and also to respond to vaccinations.”

    Further studies conducted by the researchers suggest that these B cells may arise from an alternative fetal progenitor cell distinct from the HSC — perhaps as an evolutionary effort to separate what’s known as innate immunity from adaptive immunity. They urge further research into the clinical outcomes of the transplantation of purified HSC in humans. As Ghosn said:

    “From a clinical standpoint, these findings raise the key question of whether human HSC transplantation, widely used in human regenerative therapies to restore immunity in immune-compromised patients, is sufficient to regenerate human tissue B cells that help protect transplanted patients from subsequent infectious diseases. This is specially relevant today considering that the field is moving toward using highly purified human HSCs in clinical settings.”

    More research is needed to confirm the findings in humans, however. If you’re interested in learning more about this, Ghosn expanded upon the idea earlier this month with a review in the Annals of the New York Academy of Sciences.

    See the full article here .

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  • richardmitnick 9:36 am on October 3, 2015 Permalink | Reply
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    From Wyss Institute at Harvard: “How stem-cell research has received a boost” 

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    Sep 18 2015
    Benjamin Boettner
    Kat J. McAlpine

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    Possible stem cell therapies often are limited by low survival of transplanted stem cells and the lack of precise control over their differentiation into the cell types needed to repair or replace injured tissues. A team led by David Mooney, a core faculty member at Harvard’s Wyss Institute, has now developed a strategy that has experimentally improved bone repair by boosting the survival rate of transplanted stem cells and influencing their cell differentiation. The method embeds stem cells into porous, transplantable hydrogels.

    In addition to Mooney, the team included Georg Duda, a Wyss associate faculty member and director of the Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration at Charité – Universitätsmedizin in Berlin, and Wyss Institute founding director Donald Ingber. The team published its findings in today’s issue of Nature Materials. Mooney is also the Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

    Stem cell therapies have potential for repairing many tissues and bones, or even for replacing organs. Tissue-specific stem cells can now be generated in the laboratory. However, no matter how well they grow in the lab, stem cells must survive and function properly after transplantation. Getting them to do so has been a major challenge for researchers.

    Mooney’s team and other researchers have identified specific chemical and physical cues from the stem cell niche (the area in which stem cells survive and thrive with support from other cell types and environmental factors) to promote stem cell survival, multiplication and maturation into tissue. Whereas chemical signals that control stem cell behavior are increasingly understood, much less is known about the mechanical properties of stem cell niches. Stem cells like those present in bone, cartilage, or muscle cultured in laboratories, however, have been found to possess mechanosensitivities, meaning they require a physical substrate with defined elasticity and stiffness to proliferate and mature.

    “So far these physical influences had not been efficiently harnessed to propel real-world regeneration processes,” said Nathaniel Huebsch, a graduate student who worked with Mooney and who is the study’s first author. “Based on our experience with mechanosensitive stem cells, we hypothesized that hydrogels could be leveraged to generate the right chemical and mechanical cues in a first model of bone regeneration.”

    Two water-filled hydrogels with very different properties are the key to the Mooney team’s method. A more stable, longer-lasting “bulk gel” is filled with small bubbles of a second, so-called “porogen” that degrades at a much faster rate, leaving behind porous cavities.

    By coupling the bulk gel with a small “peptide” derived from the extracellular environment of genuine stem cell niches, and mixing it with a tissue-specific stem cell type as well as the porogen, the team can create a bone-forming artificial niche. While the bulk gel provides just the right amount of elasticity plus a relevant chemical signal to coax stem cells to proliferate and mature, the porogen gradually breaks down, leaving open spaces into which the stem cells expand before they naturally migrate out of the gel structure altogether to form actual mineralized bone tissue.

    In small-animal experiments conducted so far, the researchers show that a void-forming hydrogel with the correct chemical and elastic properties provides better bone regeneration than transplanting stem cells alone. Of further interest, the maturing stem cells deployed by the hydrogel also induce nearby native stem cells to contribute to bone repair, further amplifying their regenerative effects.

    “This study provides the first demonstration that the physical properties of a biomaterial can not only help deliver stem cells but also tune their behavior in vivo,” said Mooney. “While so far we have focused on orchestrating bone formation, we believe that our hydrogel concept can be broadly applied to other regenerative processes as well.”

    The collaborative, cross-disciplinary work was supported by the Harvard University Materials Research Science and Engineering Center (MRSEC), which is funded by the National Science Foundation (NSF).

    “This is an exquisite demonstration of MRSEC programs’ high impact,” said Dan Finotello, program director at the NSF. “MRSECs bring together several researchers of varied experience and complementary expertise who are then able to advance science at a considerably faster rate.”

    Additional funding was provided by the National Institutes of Health; the Belgian American Education Foundation; the Einstein Foundation Berlin; the Berlin-Brandenburg School for Regenerative Therapies; the Harvard College Research Program; and NSF Graduate Research, Einstein Visiting, Harvard College PRISE, Herchel-Smith and Pechet Family Fund Fellowships.

    See the full article here .

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    Harvard University campus

    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 8:06 am on September 15, 2015 Permalink | Reply
    Tags: , , Stem Cell Research   

    From Harvard: “Filling a void in stem cell therapy” 

    Harvard University

    Harvard University

    Harvard  John A Paulson School of Engineering and Applied Sciences

    Sept. 14, 2015
    Harvard John A. Paulson School of Engineering and Applies Sciences
    Leah Burrows, (617) 496-1351

    Wyss Institute for Biologically Inspired Engineering at Harvard
    Kat J. McAlpine, 617-432-8266

    1

    Stem cell therapies are often limited by low survival of transplanted stem cells and the lack of precise control over their differentiation into the terminal cell types needed to repair or replace injured tissues. Now, a team led by David Mooney, the Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), has developed a new strategy – embedding stem cells into porous, transplantable hydrogels – that has experimentally improved bone repair by boosting the survival rate of transplanted stem cells and influencing their cell differentiation.

    Mooney – who is also a Core Faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard – and his team published their findings in the September 14 issue of Nature Materials. The team included Georg Duda, Ph.D., who is a Wyss Associate Faculty member and the director of the Julius Wolff Institute and Professor of Biomechanics and Musculoskeletal Regeneration at Charité – Universitätsmedizin Berlin, and Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also Professor of Bioengineering at SEAS and the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital.

    Stem cell therapies bear tremendous hopes for the repair of many tissues and bone or even the replacement of entire organs. Tissue–specific stem cells can now be generated in the laboratory. However, no matter how well they grow in the laboratory, stem cells must survive after they are transplanted and function correctly at the site of injury to be useful for clinical regenerative therapies. As of now, transplanted cell death remains a major challenge.

    To improve the therapeutic ability of transplanted stem cells, Mooney’s team has drawn inspiration from naturally occurring stem cell “niches”. A ‘stem cell niche‘ is a unique support system for stem cells consisting of other cell types and an extracellular molecular matrix that affects their fate.

    Recently, Mooney’s team as well as other researchers have identified specific chemical and physical cues from the niche that act in concert to promote stem cell survival, multiplication and maturation into tissue. Whereas chemical signals that control stem cell behavior are increasingly understood, much less is known about the mechanical properties of stem cell niches. Stem cells like those present in bone, cartilage or muscle cultured in laboratories, however, have been found to possess mechanosensitivities; meaning they require a physical substrate with defined elasticity and stiffness to proliferate and mature on.

    “So far these physical influences had not been efficiently harnessed to propel real world regeneration processes,” said Nathaniel Huebsch, a Graduate Student who worked with Mooney and who is the study’s first author. “Based on our experience with mechanosensitive stem cells, we hypothesized that hydrogels could be leveraged to generate the right chemical and mechanical cues in a first model of bone regeneration.”

    Key to the method developed by Mooney’s team is the combination of two water–filled hydrogels with very different properties. A more stable, longer lasting ‘bulk gel’ is filled with small bubbles of a second, so–called ‘porogen’ that degrades at a much faster rate, leaving behind porous cavities.

    By coupling the bulk gel with a small peptide derived from the extracellular environment of genuine stem cell niches, and mixing it with a tissue–specific stem cell type as well as the porogen, the team can create a bone–forming artificial niche. While the bulk gel provides just the right amount of elasticity plus a relevant chemical signal to coax stem cells into proliferation and send them on their maturation path, the porogen gradually breaks down, leaving open spaces for the stem cells to expand into before they naturally migrate out of the gel structure altogether to form actual mineralized bone tissue.

    In small animal experiments conducted so far, the researchers show that a void–forming hydrogel with the correct chemical and elastic properties provides better bone regeneration than transplanting stem cells alone. Of further interest, the maturing stem cells deployed by the hydrogel also induce nearby native stem cells to contribute to bone repair, thus further amplifying their regenerative effects.

    “This study provides the first demonstration that the physical properties of a biomaterial can not only help deliver stem cells but also tune their behavior in vivo,” said Mooney. “While so far we have focused on orchestrating bone formation, we believe that our hydrogel concept can be broadly applied to other regenerative processes as well.”

    The collaborative, cross–disciplinary work was supported by the Harvard University Materials Research Science and Engineering Center (MRSEC), which is funded by the National Science Foundation (NSF).

    “This is an exquisite demonstration of MRSEC programs’ high impact,” said Dan Finotello, program director at the NSF. “MRSECs bring together several researchers of varied experience and complementary expertise who are then able to advance science at a considerably faster rate.”

    Additional funding was provided by: the National Institutes of Health; the Belgian American Education Foundation; the Einstein Foundation Berlin; the Berlin-Brandenburg School for Regenerative Therapies; the Harvard College Research Program; and NSF Graduate Research, Einstein Visiting, Harvard College PRISE, Herchel-Smith and Pechet Family Fund Fellowships.

    See the full article here .

    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

     
  • richardmitnick 7:47 am on May 7, 2015 Permalink | Reply
    Tags: , , Stem Cell Research   

    From Salk: “New stem cell may overcome hurdles for regenerative medicine” 

    Salk Institute bloc

    Salk Institute for Biological Studies

    May 06, 2015
    No Writer Cedit

    Scientists at the Salk Institute have discovered a novel type of pluripotent stem cell–cells capable of developing into any type of tissue–whose identity is tied to their location in a developing embryo. This contrasts with stem cells traditionally used in scientific study, which are characterized by their time-related stage of development.

    In the paper, published May 6, 2015 in Nature, the scientists report using these new stem cells to develop the first reliable method for integrating human stem cells into nonviable mouse embryos in a laboratory dish in such a way that the human cells began to differentiate into early-stage tissues.

    2
    In this image, a novel type of human stem cell is shown in green integrating and developing into the surrounding cells of a nonviable mouse embryo. Red indicates cells of endoderm lineage. Endoderm cells can give rise to tissue that covers organs from the digestive and respiratory systems. The new stem cell, developed at the Salk Institute, holds promise for one day growing replacement functional cells and tissues. Image: Courtesy of the Salk Institute for Biological Studies.

    “The region-specific cells we found could provide tremendous advantages in the laboratory to study development, evolution and disease, and may offer avenues for generating novel therapies,” says Salk Professor Juan Carlos Izpisua Belmonte, senior author of the paper and holder of Salk’s Roger Guillemin Chair.

    The researchers dubbed this new class of cells “region-selective pluripotent stem cells,” or rsPSCs for short. The rsPSCs were easier to grow in the laboratory than conventional human pluripotent stem cells and offered advantages for large-scale production and gene editing (altering a cell’s DNA), both desirable features for cell replacement therapies.

    To produce the cells, the Salk scientists developed a combination of chemical signals that directed human stem cells in a laboratory dish to become spatially oriented.

    They then inserted the spatially oriented human stem cells (human rsPSCs) into specific regions of partially dissected mouse embryos and cultured them in a dish for 36 hours. Separately, they also inserted human stem cells cultured using conventional methods, so that they could compare existing techniques to their new technique.

    While the human stem cells derived through conventional methods failed to integrate into the modified embryos, the human rsPSCs began to develop into early stage tissues. The cells in this region of an early embryo undergo dynamic changes to give rise to all cells, tissues and organs of the body. Indeed the human rsPSCs began the process of differentiating into the three major cell layers in early development, known as ectoderm, mesoderm and endoderm. The Salk researchers stopped the cells from differentiating further, but each germ layer was theoretically capable of giving rise to specific tissues and organs.

    3
    Juan Carlos Izpisua Belmonte and Jun Wu. Image: Courtesy of the Salk Institute for Biological Studies

    Collaborating with the labs of Salk Professors Joseph Ecker and Alan Saghatelian, the Izpisua Belmonte team performed extensive characterization of the new cells and found rsPSCs showed distinct molecular and metabolic characteristics as well as novel epigenetic signatures–that is, patterns of chemical modifications to DNA that control which genes are turned on or off without changing the DNA sequence.

    “The region selective-state of these stem cells is entirely novel for laboratory-cultured stem cells and offers important insight into how human stem cells might be differentiated into derivatives that give rise to a wide range of tissues and organs,” says Jun Wu, a postdoctoral researcher in Izpisua Belmonte’s lab and first author of the new paper. “Not only do we need to consider the timing, but also the spatial characteristics of the stem cells. Understanding both aspects of a stem cell’s identity could be crucial to generate functional and mature cell types for regenerative medicine.”

    4
    The new stem cell (green), developed at the Salk Institute, holds promise for one day growing replacement functional cells and tissues.
    Image: Courtesy of the Salk Institute for Biological Studies.

    Other authors on the paper include: Daiji Okamura, Mo Li, Keiichiro Suzuki, Li Ma, Zhongwei Li, Chris Benner, Isao Tamura, Marie N. Krause, Joseph R. Nery, Zhuzhu Zhang, Tomoaki Hishida, Yuta Takahashi, Emi Aizawa, Na Young Kim, Concepcion Rodriguez Esteban, Alan Saghatelian, Joseph Ecker, Chongyuan Luo, Yupeng He, all of the Salk Institute; Tingting Du, and Bing Ren of the University of California, San Diego; Jeronimo Lajara and Pedro Guillen, of UCAM Universidad Católica San Antonio, Murcia, Spain; Josep M. Campistol, Hospital Clinic of Barcelona, Spain; and Pablo Ross of the University of California, Davis.

    The research was supported by the Universidad Católica San Antonio, the Howard Hughes Medical Institute, the Fundacion Pedro Guillen, the G. Harold and Leila Y. Mathers Charitable Foundation, the Leona M. and Harry B. Helmsley Charitable Trust and the Moxie Foundation.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Salk Institute Campus

    Every cure has a starting point. Like Dr. Jonas Salk when he conquered polio, Salk scientists are dedicated to innovative biological research. Exploring the molecular basis of diseases makes curing them more likely. In an outstanding and unique environment we gather the foremost scientific minds in the world and give them the freedom to work collaboratively and think creatively. For over 50 years this wide-ranging scientific inquiry has yielded life-changing discoveries impacting human health. We are home to Nobel Laureates and members of the National Academy of Sciences who train and mentor the next generation of international scientists. We lead biological research. We prize discovery. Salk is where cures begin.

     
  • richardmitnick 12:46 pm on April 8, 2015 Permalink | Reply
    Tags: , , Stem Cell Research   

    From Rice: “Amniotic stem cells demonstrate healing potential” 

    Rice U bloc

    Rice University

    April 8, 2015
    Mike Williams

    Rice University and Texas Children’s Hospital scientists are using stem cells from amniotic fluid to promote the growth of robust, functional blood vessels in healing hydrogels.

    In new experiments, the lab of bioengineer Jeffrey Jacot combined versatile amniotic stem cells with injectable hydrogels used as scaffolds in regenerative medicine and proved they enhance the development of vessels needed to bring blood to new tissue and carry waste products away.

    The results appear in the Journal of Biomedical Materials Research Part A.

    Jacot and his colleagues study the use of amniotic fluid cells from pregnant women to help heal infants born with congenital heart defects. Such fluids, drawn during standard tests, are generally discarded but show promise for implants made from a baby’s own genetically matched material.

    He contends amniotic stem cells are valuable for their ability to differentiate into many other types of cells, including endothelial cells that form blood vessels.

    1
    A microscope image shows mature blood vessels that formed in a hydrogel after two weeks of growth in a mouse model, with red blood cells flowing through the vessel at bottom right. The vessels form from stem cells derived from amniotic fluid in a technique created by the lab of Rice University and Texas Children’s Hospital bioengineer Jeffrey Jacot. The scale bar is 100 microns. Courtesy of the Jacot Lab

    “The main thing we’ve figured out is how to get a vascularized device: laboratory-grown tissue that is made entirely from amniotic fluid cells,” Jacot said. “We showed it’s possible to use only cells derived from amniotic fluid.”

    2
    A hydrogel seeded with amniotic fluid stem cells shows the growth of mature blood vessels two weeks after implantation in an experiment by researchers at Rice University and Texas Children’s Hospital. The cell nuclei are blue, endothelial cells are red and smooth muscle cells are green. The scale bar is 20 microns. Courtesy of the Jacot Lab

    In the lab, researchers from Rice, Texas Children’s Hospital and Baylor College of Medicine combined amniotic fluid stem cells with a hydrogel made from polyethylene glycol and fibrin. Fibrin is a biopolymer critical to blood clotting, cellular-matrix interactions, wound healing and angiogenesis, the process by which new vessels branch off from existing ones. Fibrin is widely used as a bioscaffold but suffers from low mechanical stiffness and rapid degradation. Combining fibrin and polyethylene glycol made the hydrogel much more robust, Jacot said.

    The lab used vascular endothelial growth factor to prompt stem cells to turn into endothelial cells, while the presence of fibrin encouraged the infiltration of native vasculature from neighboring tissue.

    Mice injected with fibrin-only hydrogels showed the development of thin fibril structures, while those infused with the amniotic cell/fibrin hydrogel showed far more robust vasculature, according to the researchers.

    Similar experiments using hydrogel seeded with bone marrow-derived mesenchymal cells also showed vascular growth, but without the guarantee of a tissue match, Jacot said. Seeding with endothelial cells didn’t work as well as the researchers expected, he said.

    3
    The lab of Rice University and Texas Children’s Hospital bioengineer Jeffrey Jacot has successfully used stem cells derived from amniotic fluid to promote the growth of functional blood vessels in an injectable hydrogel. Photo by Jeff Fitlow

    The lab will continue to study the use of amniotic cells to build biocompatible patches for the hearts of infants born with birth defects and for other procedures, Jacot said.

    Rice alumnus Omar Benavides, now a senior product development engineer at Procyrion, is lead author of the paper. Co-authors are Rice undergraduates Abigail Brooks and Sung Kyung Cho; Rice alumnus Jennifer Petsche Connell, now a researcher at Houston Methodist Hospital Research Institute, and Rodrigo Ruano, co-director of the Texas Children’s Hospital Fetal Center and a professor at Baylor College of Medicine.

    Jacot is an associate professor of bioengineering at Rice, director of the Pediatric Cardiac Bioengineering Laboratory at the Congenital Heart Surgery Service at Texas Children’s and an adjunct assistant professor at Baylor College of Medicine.

    The National Institutes of Health and the National Science Foundation supported the research.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Rice U campus

    In his 1912 inaugural address, Rice University president Edgar Odell Lovett set forth an ambitious vision for a great research university in Houston, Texas; one dedicated to excellence across the range of human endeavor. With this bold beginning in mind, and with Rice’s centennial approaching, it is time to ask again what we aspire to in a dynamic and shrinking world in which education and the production of knowledge will play an even greater role. What shall our vision be for Rice as we prepare for its second century, and how ought we to advance over the next decade?

    This was the fundamental question posed in the Call to Conversation, a document released to the Rice community in summer 2005. The Call to Conversation asked us to reexamine many aspects of our enterprise, from our fundamental mission and aspirations to the manner in which we define and achieve excellence. It identified the pressures of a constantly changing and increasingly competitive landscape; it asked us to assess honestly Rice’s comparative strengths and weaknesses; and it called on us to define strategic priorities for the future, an effort that will be a focus of the next phase of this process.

     
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