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	Forscher erschaffen Rattenlunge Sonntag, 27. Juni 2010 Forscher erschaffen eine Rattenlunge und lösen sie dafür zuerst auf, bis nur noch das Gerüst übrig bleibt. Forscher haben eine halb künstliche und halb natürliche Rattenlunge geschaffen. Sie half dabei, Versuchstiere bis zu zwei Stunden mit Sauerstoff zu versorgen. Die Lungen wurden für das Experiment drastisch behandelt: Eine Lösung entfernte binnen Stunden alle Zellen daraus, bis nur noch ein feines Kollagen-Gerüst in Lungenform zurückblieb. Danach hängte das Team um Thomas Petersen von der Yale University in New Haven diesen filigranen Rest in einen Bioreaktor, um ihn mit einem Nährmedium zu umspülen. Hinzugefügte Lungenzellen, ebenfalls aus Ratten gewonnen, besiedelten das Gerüst schließlich wieder, schreibt das Team im Journal "Science". Die Experimente finden nicht vor dem Hintergrund eines Horrorfilmes statt, sondern sollen eines fernen Tages dem verbreiteten Mangel an Spenderorganen abhelfen. Menschliches Lungengewebe hat nur eine begrenzte Fähigkeit zur Regeneration. Transplantationen sind daher oft das letzte Mittel, um Patienten überhaupt helfen zu können – aber dazu mangelt es an passenden Spendern. Zudem überleben nur 10 bis 20 Prozent der Transplantierten länger als 10 Jahre, schreiben die Forscher. Besser wäre es daher, eine Lunge mit den Zellen des Patienten nachzubauen - etwa, indem ein dreidimensionales Lungengerüst dafür besiedelt wird. Künstliches Organ wird Ratten implantiert Die Lunge versorgt das Blut mit Sauerstoff und entfernt Kohlendioxid daraus. Dafür ist ihre innere Oberfläche rund 70 Quadratmeter groß. Sie trennt die Atemluft mit einer hauchfeinen Barriere vom Blutfluss und ermöglicht den Gasaustausch. Das entleerte Lungengerüst aus Bindegewebe wurde innerhalb etwa einer Woche neu besiedelt. Der ultimative Test war es schließlich, diese künstlichen Organe in Versuchstiere zu implantierten und sie in den Blutkreislauf einzugliedern. Dafür wurde jeweils nur ein Lungenflügel eingesetzt, der sich im Körper nicht zur gleichen Größe entfaltete wie das Original. Beim Vergleich des Blutflusses zwischen den beiden Lungenflügeln zeigte sich, dass auch das Blut aus der neuen Lunge ebenfalls mit Sauerstoff gesättigt war. Länger als zwei Stunden wurde die neue Lunge aber nicht getestet. Versuch mit menschlichem Gewebe Das Team um Petersen organisierte aus einer Gewebebank auch menschliches Lungengewebe, behandelte es ganz ähnlich und ließ es gleichfalls von menschlichen Zellen neu besiedeln. Dies funktionierte, die Zellen lagerten sich an. Prinzipiell lasse dies erwarten, dass entsprechende Experimente auch beim Menschen funktionieren könnten. In diesem Fall müsste ein Gerüst mit Stammzellen des Patienten besiedelt werden, damit das so heranwachsende Organ im Organismus nicht abgestoßen würde.

	Retina Created from Human Embryonic Stem Cells ScienceDaily (May 27, 2010) — UC Irvine scientists have created an eight-layer, early stage retina from human embryonic stem cells, the first three-dimensional tissue structure to be made from stem cells. It also marks the first step toward the development of transplant-ready retinas to treat eye disorders such as retinitis pigmentosa and macular degeneration that affect millions. "We made a complex structure consisting of many cell types," said study leader Hans Keirstead of the Reeve-Irvine Research Center and the Sue and Bill Gross Stem Cell Research Center at UCI. "This is a major advance in our quest to treat retinal disease." In previous studies on spinal cord injury, the Keirstead group originated a method by which human embryonic stem cells could be directed to become specific cell types, a process called differentiation. Results of those studies are leading to the world's first clinical trial using a stem cell-based therapy for acute spinal cord injury. In this study, the Keirstead team utilized the differentiation technique to create the multiple cell types necessary for the retina. The greatest challenge, Keirstead said, was in the engineering. To mimic early stage retinal development, the researchers needed to build microscopic gradients for solutions in which to bathe the stem cells to initiate specific differentiation paths. "Creating this complex tissue is a first for the stem cell field," Keirstead said. "Dr. Gabriel Nistor in our group addressed a really interesting scientific problem with an engineering solution, showing that gradients of solutions can create complex stem cell-based tissues." The retina is the inside back layer of the eye that records the images a person sees and sends them via the optic nerve from the eye to the brain. Retinal diseases are particularly damaging to sight. More than 10 million Americans suffer from macular degeneration, the leading cause of blindness in people over 55. About 100,000 have retinitis pigmentosa, a progressive, genetic disorder that usually manifests in childhood. "What's so exciting with our discovery," Keirstead said, "is that creating transplantable retinas from stem cells could help millions of people, and we are well on the way." The UCI researchers are testing the early-stage retinas in animal models to learn how much they improve vision. Positive results would lead to human clinical trials. The study appears online in the Journal of Neuroscience Methods. Nistor, Magdalene J. Seiler, Fengrong Yan and David Ferguson contributed to the effort, supported by The Lincy Foundation and private donations to the Keirstead group.

	Parvovirus kills brain cancer cells - Human trials to start soon ScienceDaily (May 5, 2010) — Particular parvoviruses normally infect rodents, but they are also infectious for human cells. However, they do not cause any disease symptoms in humans. Most importantly, these viruses have an astonishing property: They kill infected tumors cells without causing any damage to healthy tissue. Therefore, scientists in the teams of Jean Rommelaere and Jörg Schlehofer at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have been investigating over the past years whether these viruses can be used as weapons against cancer. Many different viruses have been tested before in cancer therapy, particularly for treating those types of cancer for which there are no effective established treatment methods. The DKFZ researchers realized early on that parvovirus H-1 has important advantages over other viruses. Now they have been the first to prove that malignant glioblastomas regress completely as a result of treatment with these viruses. The treatment experiments were conducted in rats who had received brain tumors cells by implantation. Once the resulting brain tumors had reached a specified size, the animals were given parvoviruses, either by direct injection into the tumor or via the blood stream. In those animals in which the viruses had been injected directly into the tumor, the tumors shrank visibly after only three days and even disappeared completely in eight of twelve animals treated. The rodents survived without any symptoms, while untreated control animals suffered from severe disease symptoms within three weeks following tumor cell implantation. In the intravenously treated group, tumors regressed completely in six of nine animals. The animals have survived for more than one year now without any symptoms or late side effects of therapy. The researchers found no infection-related damage in the nervous tissue surrounding the tumor. The viruses did not spread to the whole organism. Although parvovirus DNA was detectable in all organs after several days following virus transfer, this was only for a short time. The viruses had infected healthy cells, but these did not produce a new virus generation. However, in the tumor tissue, the viruses reproduced and viral protein production was detected only in these cells. In rats that did not bear tumors, the viruses did not reproduce. Thus, it appears that the presence of cancer cells is a necessary condition for the parvoviruses to reproduce. After the positive results of these experiments the DKFZ researchers are convinced that parvoviruses are suitable candidates for use in cancer treatment. Professor Jean Rommelaere summarizes the reasons why: "Parvovirus H-1 does not cause any disease symptoms in humans. Since we are normally not immune against rodent viruses, it is not immediately eliminated by the human immune system after injection. Parvoviruses kill tumors due to natural properties so that their genetic material does not need to be genetically manipulated like herpes viruses, polio viruses or adenoviruses, which have been used in other studies. Moreover, they do not incorporate their genetic material into the host cell's genome, so we need not fear that they might 'accidentally' boost growth-promoting genes." Rommelaere's colleague, Jörg Schlehofer, adds two more qualities that could be decisive for therapy of glioblastomas, in particular: "Parvoviruses pass the blood brain barrier so that they can be administered via the blood stream. In addition, they reproduce in cancer cells, which is particularly important for successful treatment of glioblastoma with its diffuse growth. Thus, the second generation viruses reach and eliminate even those cancer cells that have already settled at some distance from the primary tumor." Parvovirus therapy to be tested in clinical trial The promising results in the animal model have encouraged the DKFZ scientists, jointly with Dr. Karsten Geletneky of the Neurosurgery Department of Heidelberg University, to plan a clinical trial on the treatment of advanced glioblastomas. Glioblastoma is considered the most threatening type of brain tumor; only about half of those affected survive the first year after diagnosis. Even innovative drugs that have been made available recently can prolong survival only marginally. Therefore, new treatment approaches for this type of cancer are urgently needed. Many of the required toxicological data have already been obtained and submitted to the drug approval authority by the researchers so that they expect to be able to admit the first patients to the trial by the end of the year. In addition, DKFZ and Oryx have recently signed another agreement: Oryx will also get involved in the development of a parvovirus therapy against pancreatic cancer.

	Stem Cell Therapy Halts Acute Lung Damage in Mice April 16, 2010 Stem cell researchers exploring a new approach for the care of respiratory diseases report that an experimental treatment involving transplantable lung cells was associated with improved outcomes in tests on mice with acute lung injury. The lung cells were derived from human embryonic stem cells. Findings by investigators at The University of Texas Health Science Center at Houston appeared in the March issue of Molecular Therapy. Mice receiving the transplantable lung cells lived longer, sustained less scarring in their lungs, and had normal amounts of oxygen in their blood, said Rick Wetsel, Ph.D., the study's senior author and a professor in the university's Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases. During this week's podcast Dr. Wetsel provides additional details about his team's study. He also discusses why the group chose to transplant a specific type of lung cell, known as alveolar epithelial type II, and explains how the scientists went about generating these lung cells. In addition, Dr. Wetsel talks about the specific research questions that still need to be addressed before this technique finds applications in human clinical studies.

	Protein Shown to Be Natural Inhibitor of Aging ScienceDaily (Mar. 5, 2010) — Scientists at the University of California, San Diego School of Medicine, have identified a protein called Sestrin that serves as a natural inhibitor of aging and age-related pathologies in fruit flies. They also showed that Sestrin, whose structure and biochemical function are conserved between flies and humans, is needed for regulation of a signaling pathway that is the central controller of aging and metabolism. The work, led by Michael Karin, PhD, Distinguished Professor of Pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, is the cover story of the March 5 issue of the journal Science.

	Stanford scientists convert skin cells to neurons Skin cells turned into brain cells while bypassing embryonic state January 27, 2010. www.startribune.com Cells from mouse tails were manipulated into neurons able to form connections crucial to brain function. In a feat of biological alchemy, scientists at Stanford have turned the skin cells of a mouse into brain cells without ever taking the cells back to the embryonic state, raising hopes that medicine may be approaching a new era. The work by scientists at Stanford University was described in a paper published online Wednesday in the journal Nature, and builds on the 2007 discovery that human skin cells could be reprogrammed back to the embryonic state. The reprogramming of human cells was first accomplished by the labs of James Thomson at the University of Wisconsin-Madison and Shinya Yamanaka at Kyoto University in Japan. "To me, this is huge progress for biomedical science," said Su-Chun Zhang, a University of Wisconsin stem cell researcher and professor of anatomy and neurology. Zhang said the technique could one day allow doctors to treat a patient who has lost a certain kind of brain cell by converting other cells already in the patient's brain. This would be much simpler than current techniques. "This is a long-awaited breakthrough. It makes the prospect realistic that any cell type can be converted into any other, once the magic combination of transcription factors is known," said Thomas Graf, a stem cell scientist at the Center for Genomic Regulation in Barcelona, Spain, who was not involved in the Nature paper. The scientists at Stanford used techniques pioneered by Yamanaka and Thomson, searching for genes that can be inserted into one kind of cell to convert it into another kind. So far, master regulators called transcription factors have proved to be the best candidates. The Stanford researchers were able to accomplish the change from mouse skin cell to neuron by inserting three transcription factors.

	Harvard researchers reverse aging of blood system Harvard Magazine, January 27, 2010 AGING IN THE BLOOD SYSTEM can be reversed, Amy Wagers, an associate professor of stem-cell and regenerative biology, reports in the January 28 issue of Nature. The paper details findings of Wagers’s investigation of how aging and tissue repair work in the body—work described in “A Hidden Youthfulness,” the sidebar to the article on the state of stem-cell science in the January-February issue of Harvard Magazine. When Wagers joined the circulation of a young mouse to that of an old mouse for her experiment, she found that the blood stem cells in the old mouse could be reawakened to repair muscle damage efficiently—the same way the process occurs in young mice. In her Nature paper, Wagers describes what is happening at the cellular level: In old mice, blood stem cells proliferate, but paradoxically, that doesn’t improve their regenerative capacity. In fact, they become less effective and produce “too many inflammatory factors” and too few b-lymphocytes—a type of immune cell. Wagers discovered that the blood stem cells get their marching orders from osteoblasts, a bone-forming progenitor cell that lives in bone marrow. The signal sent from the osteoblasts to the blood stem cells has not yet been identified, but Wagers found that osteoblasts exposed to an aged circulation or to aging itself produce more IGF-1 (insulin-like growth factor) and respond more to that factor as well, causing “detrimental changes in that cell that are subsequently communicated to blood stem cells.” Interestingly, when IGF-1 is localized in muscle, it actually enhances repair there (as dopers in professional sport have discovered); but it seems to have the opposite effect in the blood system.

	Vaccine implant eradicates melanoma in mice Implant-Based Cancer Vaccine Is First to Eliminate Tumors in Mice ScienceDaily (Nov. 26, 2009) — A cancer vaccine carried into the body on a carefully engineered, fingernail-sized implant is the first to successfully eliminate tumors in mammals, scientists recently reported in the journal Science Translational Medicine. The new approach, pioneered by bioengineers and immunologists at Harvard University, uses plastic disks impregnated with tumor-specific antigens and implanted under the skin to reprogram the mammalian immune system to attack tumors. The new paper describes the use of such implants to eradicate melanoma tumors in mice. "This work shows the power of applying engineering approaches to immunology," says David J. Mooney, the Robert P. Pinkas Family Professor of Bioengineering in Harvard's School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering. "By marrying engineering and immunology through this collaboration with Glenn Dranoff at the Dana-Farber Cancer Institute, we've taken a major step toward the design of effective cancer vaccines." Most cancer cells easily skirt the immune system, which operates by recognizing and attacking invaders from outside the body. The approach developed by Mooney's group redirects the immune system to target tumors, and appears both more effective and less cumbersome than other cancer vaccines currently in clinical trials. Conventional cancer vaccinations remove immune cells from the body, reprogram them to attack malignant tissues, and return them to the body. However, more than 90 percent of reinjected cells have died before having any effect in experiments. The slender implants developed by Mooney's group are 8.5 millimeters in diameter and made of an FDA-approved biodegradable polymer. Ninety percent air, the disks are highly permeable to immune cells and release cytokines, powerful recruiters of immune-system messengers called dendritic cells. These cells enter an implant's pores, where they are exposed to antigens specific to the type of tumor being targeted. The dendritic cells then report to nearby lymph nodes, where they direct the immune system's T cells to hunt down and kill tumor cells. "Inserted anywhere under the skin -- much like the implantable contraceptives that can be placed in a woman's arm -- the implants activate an immune response that destroys tumor cells," Mooney says. The technique may have powerful advantages over surgery and chemotherapy, and may also be useful in combination with existing therapies. It only targets tumor cells, avoiding collateral damage elsewhere in the body. And, much as an immune response to a bacterium or virus generates long-term resistance, researchers anticipate cancer vaccines will generate permanent and body-wide resistance against cancerous cells, providing durable protection against relapse. Mooney says the new approach's strength lies in its ability to simultaneously regulate the two arms of the human immune system: one that destroys foreign material and one that protects tissue native to the human body. The implant-based vaccine recruits several types of dendritic cells that direct destructive immune responses, creating an especially potent anti-tumor response. "This approach is able to simultaneously upregulate the destructive immune response to the tumor while downregulating the arm of the immune system that leads to tolerance," Mooney says. "In cancer, this latter arm is typically a limiting feature of immunotherapies, since it can extinguish vaccine activity and afford tumors a degree of protection." Mooney's co-authors are Omar A. Ali of Harvard's School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering and InCytu, Inc.; Dwaine Emerich of InCytu, Inc.; and Glenn Dranoff of Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School. Their work was supported by the National Institutes of Health, Harvard University, and InCytu, Inc.

	Efficiency of iPS creation improved 200fold 19.10.09 A team led by scientists from The Scripps Research Institute has developed a method that dramatically improves the efficiency of creating stem cells from human adult tissue, without the use of embryonic cells. The research makes great strides in addressing a major practical challenge in the development of stem-cell-based medicine. The findings were published in an advance, online issue of the journal Nature Methods on October 18, 2009. The new technique, which uses three small drug-like chemicals, is 200 times more efficient and twice as fast as conventional methods for transforming adult human cells into stem cells (in this case called "induced pluripotent stem cells" or "iPS cells"). "Both in terms of speed and efficiency, we achieved major improvements over conventional conditions," said Scripps Research Associate Professor Sheng Ding, Ph.D., who led the study. "This is the first example in human cells of how reprogramming speed can be accelerated. I believe that the field will quickly adopt this method, accelerating iPS cell research significantly."

	Gene therapy cures ALD 5.11.09 Two 7-year-old boys with a fatal brain disease called ALD (adrenoleukodystrophy) who couldn’t get bone marrow transplants were saved by scientists whose gene therapy technique may let doctors treat other incurable disorders. Doctors in Paris delivered the gene into the boys’ bodies using HIV, the virus that causes AIDS. The virus, stripped of genetic material that makes it toxic, integrates permanently into the DNA of cells it enters, scientists said. That means the modified gene remains in the blood-forming stem cells for the life of the patient, according to a report in the journal Science. Two years after the experimental treatment, the neural damage has been halted or reversed and the two boys attend school and lead normal lives, said Nathalie Cartier, the study’s lead author. The treatment was cited as an example of a “comeback for gene therapy,” after years of setbacks, in an editorial in the journal. “Their disease is completely stabilized, they are fine and there’s no reason this should change,” Cartier, research director at the French National Institute for Health and Medical Research in Paris, said in a telephone interview yesterday. If more studies confirm the results, she said, “We think gene therapy could become a first-line treatment. It’s definitely a strategy that could be applied to other conditions.” Today’s report “represents a long-sought rewarding achievement in the field of gene therapy,” wrote Luigi Naldini, a researcher in Milan, Italy, in the editorial accompanying the study.

	Major Breakthrough In Generating Safer, Therapeutic Stem Cells From Adult Cells Researchers have developed a new technique for converting adult cells all the way back to the most primitive embryonic-like cells without using the dangerous genetic manipulations associated with previous methods. The new technique solves one of the most challenging safety hurdles associated with personalized stem cell-based medicine because for the first time it enables scientists to make stem cells in the laboratory from adult cells without genetically altering them. This discovery has the potential to spark the development of many new types of therapies for humans, for diseases that range from Type 1 diabetes to Parkinson's disease. The study was published in an advance, online issue of the journal Cell Stem Cell on April 23, 2009. "We are very excited about this breakthrough in generating embryonic-like cells from fibroblasts [cells that gives rise to connective tissue] without using any genetic material," says Scripps Research Associate Professor Sheng Ding, who led the research. "Scientists have been dreaming about this for years." Normally, cells develop from stem cells into a myriad of increasingly more specialized cell types during early development and throughout a lifetime. In humans and other mammals, these developmental events are irreversible. This means that when tissues are damaged or cells are lost, there is usually no source from which to replenish them. Having a source of the most primitive stem cells available would be useful in many medical situations because these cells are "pluripotent," having the ability to become any of the body's cell types—potentially providing doctors with the ability to repair damaged tissues throughout the body. However bright this promise, the use of stem cells in medicine has faced many hurdles. One strategy has been to work towards a therapy where doctors could take a patient's own adult cells and "reprogram" them into stem cells. This not only avoids potential ethical problems associated with the use of human embryonic stem cells, it also addresses concerns about compatibility and immune rejection that plague therapies such as organ transplantation. A few years ago, a team of researchers in Japan made a breakthrough in this general approach by converting mouse skin cells into mouse stem cells. The Japanese team accomplished this remarkable transformation by inserting a set of four genes into these skin cells. While the study was a powerful proof-of-principle, the therapeutic potential of genetically reprogrammed cells is limited because of safety issues. One obvious problem is that the four required genes and their associated foreign DNA sequences permanently reside in the cells when transplanted. Moreover, the specific genes in question are problematic because, in living tissue, they are linked to the development of cancerous tumors. Many scientists have been trying to find safer ways to generate stem cells from adult cells -- developing methods that require fewer genes, or techniques that can put genes in and then take them out. However, to date all of these have still harbored significant safety concerns due to the nature of the genetic manipulations. Ding and his team previously reported the discovery of drug-like small molecules to replace some of those genes, but have also hoped to go even further and find ways to reprogram adult cells into stem cells without using any genes or genetic manipulations at all. The team of scientists accomplished this extraordinarily challenging feat by engineering and using recombinant proteins, that is proteins made from the recombination of fragments of DNA from different organisms. Many different recombinant proteins have been therapeutically and routinely used to treat human diseases. Instead of inserting the four genes into the cells they wanted to reprogram, the scientists added the purified engineered proteins and experimented with the chemically defined conditions without any genetic materials involved until they found the exact mix that allowed them to gradually reprogram the cells. The scientists found that those reprogrammed embryonic-like cells (dubbed "protein-induced pluripotent stem cells" or "piPS cells") from fibroblasts behave indistinguishably from classic embryonic stem cells in their molecular and functional features, including differentiation into various cell types, such as beating cardiac muscle cells, neurons, and pancreatic cells. The first author of the article, "Generation of Induced Pluripotent Stem Cells Using Recombinant Proteins" was Hongyan Zhou of Scripps Research. In addition to Ding and Zhou, authors of the paper include Shili Wu, Geoffery Bien, Susan Yao, and Yong Zhu of ProteomTech Inc. (Costa Mesa, CA); Jinyoung Joo, Dong Wook Han, and Hans R. Schöler of the Max Planck Institute for Molecular Biomedicine (Germany); Lingxun Duan of LD Biopharma, Inc. (San Diego); and Saiyong Zhu, Tongxiang Lin, Sunia Trauger, and Gary Siuzdak of Scripps Research.

	Large Quantity Of Stem Cells Produced From Small Number Of Blood Stem Cells ScienceDaily (Apr. 17, 2009) — A team from the Institute for Research in Immunology and Cancer (IRIC) at Université de Montréal has succeeded in producing a large quantity of laboratory stem cells from a small number of blood stem cells obtained from bone marrow. The multidisciplinary team, directed by Dr. Guy Sauvageau, thus took a giant step towards the development of a revolutionary treatment based on these stem cells. This worldwide first will advance stem cell research and could have major implications in several fields for which no treatment currently exists. Every year in North America, nearly 4,000 people wait in vain for a bone marrow transplant due to the lack of compatible donors. It is known that a bone marrow stem cell transplant can reconstitute the recipient's bone marrow. The main difficulty is to obtain a sufficient number of compatible stem cells. Thanks to Dr. Sauvageau and his team, these patients will be able to obtain new bone marrow within the next few years. "It could be possible to envision transplants for all adults from existing umbilical cord blood banks. The stem cell content of these blood banks is currently too limited for large-scale use in adults," Dr. Sauvageau affirmed. Organ transplants without side effects: the medicine of the future? Currently, transplant recipients are condemned to take medications against rejection of the transplanted organ and suffer the side effects for the rest of their lives. However, "mouse studies exist, showing that bone marrow stem cells can prevent the rejection typically directed against solid organs," Dr. Sauvageau said. Rejection occurs because the immune system cells manufactured by bone marrow attack the transplanted organ as if it were an invader. By extrapolation from laboratory studies, it is very likely that transplanting hematopoietic stem cells collected from the organ donor and developed in the laboratory could avoid rejection of this organ. This is why it is important to have large quantities of hematopoietic stem cells, so that compatible stem cells can be matched with the organ to be transplanted. Using proteins to multiply stem cells To produce large quantities of hematopoietic stem cells in the laboratory, Dr. Sauvageau's team identified 10 proteins out of 700 candidates. These 10 proteins are naturally present in hematopoietic stem cells and researchers can use each of them to force these cells to multiply in the laboratory. "The next step is to verify whether this also works in humans. Everything is already in place," Guy Sauvageau pointed out. These tests will be conducted at Montreal's Maisonneuve-Rosemont Hospital, one of the leading centres in Canada where stem cell transplants are performed. "If only one of the ten proteins allows hematopoietic stem cells to be multiplied in humans, we will be able to obtain the quantities of cells necessary to perform transplants. It will then be possible to say "mission accomplished"." Researchers around the world are currently trying to harness the regenerative power of other types of stem cells to treat diseases such as Alzheimer's or diabetes. IRIC's research could also help them achieve their goal. The work of Dr. Sauvageau's team has been funded by the Canadian Institutes of Health Research and the findings are published April 16 in the journal Cell.

	ETH-Forscher bauen Bakterien nach 7.4.2009 ETH-Forscher haben Mikro-Roboter gebaut, die erstmals so klein sind wie Bakterien. Diese sollen helfen, Menschen zu heilen. Artificial Bacterial Flagella sind etwa halb so lang wie ein menschliches Haar dick ist. Sie können sich mit einer Geschwindigkeit von bis zu einer Körperlänge pro Sekunde fortbewegen. Damit kommen sie ihren Vorbildern aus der Natur schon sehr nahe. (Bild: Institut für Robotik und Intelligente Systeme/ETH Zürich) Sie sehen aus wie Spiralen mit kleinem Köpfchen und schrauben sich wie Miniatur-Korkenzieher durch die Flüssigkeit. In Bewegung wirken sie wie etwas plumpe Bakterien mit langen Geisseln. Beobachten lassen sie sich nur unter dem Mikroskop, denn sie sind mit ihren 25 bis 60 µm Gesamtlänge fast so winzig wie natürliche Geisseln tragende Bakterien. Die sind meist zwischen 5 und 15 µm lang, einige über 20 µm. Der Natur abgeschaut Die kleinen schraubenförmigen, der Natur abgeschauten Plagiate von E.coli und Co heissen «Artificial Bacterial Flagella» (ABF), was auf Deutsch etwa so viel heisst wie «künstliche begeisselte Bakterien». Erfunden, hergestellt und zum Schwimmen gebracht haben sie Forscher der Gruppe von Bradley Nelson, Professor am Institut für Robotik und Intelligente Systeme an der ETH Zürich. Im Gegensatz zu ihren in der Natur vorkommenden Vorbildern, die zum Teil Krankheiten auslösen, sollen die ABFs in Zukunft helfen, Krankheiten zu heilen. Die Realisierung dieser bisher kleinsten künstlichen Bakterien mit starrer Geissel und externem Antrieb war vor allem durch das Material möglich, aus dem die schraubenförmigen ABFs bestehen. Für die Herstellung der ABFs werden verschiedene dünnste Schichten aus den Elementen Indium, Galium, Arsen und Chrom in bestimmter Reihenfolge auf eine Unterlage aufgedampft. Am Schluss werden sie durch Ätzen wieder abgelöst. So entstehen superdünne, schmale, sehr lange Rechtecke. Diese drehen sich, sobald sie losgelöst werden, wegen der ungleichen Molekülgitter der verschiedenen Schichten, selbst in die Spiralform. Je nach aufgebrachter Schichtdicke und Zusammensetzung entsteht eine leicht andere, aber von den Forschern genau definierbare, Spirale. «Wir können nicht nur bestimmen, wie eng die Spirale wird, sondern auch in welche Richtung sie sich drehen soll», sagt Nelson. Externer Antrieb durch Magnetfeld Noch vor dem Ablösen des Streifens, der nachher die künstliche Geissel bildet, wird an dessen einem Ende eine Art Kopf für den Mini-Roboter angebracht. Er besteht aus einem Chrom-Nickel-Gold-Film, der ebenfalls aufgedampft wird. Nickel ist, im Gegensatz zu den anderen eingesetzten, nicht magnetischen Materialien, schwach magnetisch. «Dieses magnetische Köpfchen ermöglicht es, das ABF in einem Magnetfeld gezielt zu bewegen», erklärt Nelson. Das spiralförmige ABF schraubt sich durch die Flüssigkeit. Seine Bewegungen können unter dem Mikroskop nachverfolgt und gefilmt werden. Mit der Software, die die Gruppe entwickelt hat, lässt sich das ABF durch Veränderungen an der Stärke und Richtung des durch mehrere Spulen aufgebauten rotierenden Magnetfeldes, ganz gezielt auf ein Ziel zubewegen. Die ABFs können sich vorwärts und rückwärts, nach oben und unten bewegen. Sie können auch in alle Richtungen rotieren. «Da ist eine Menge Physik und Mathematik hinter der Software», sagt Brad Nelson. Für die Fortbewegung brauchen die ABFs weder eigene Energie noch haben sie bewegliche Teile. Entscheidend ist alleine das Magnetfeld, an dessen Richtung sich das Köpfchen stets anpassen möchte und in dessen Richtung es sich bewegt. Bisher schwimmen ABFs mit einer Geschwindigkeit von bis zu 20 µm pro Sekunde, das heisst bis zu einer Körperlänge pro Sekunde. Nelson erwartet, dass sich die Geschwindigkeit auf über 100 µm pro Sekunde steigern lässt. Zum Vergleich: E.coli schwimmt 30 µm pro Sekunde. Mögliche Anwendungen in der Medizin Die ABFs sollen in der Biomedizin eingesetzt werden. Sie könnten zum Beispiel Medikamente an vorher definierte Ziele im Körper bringen, Verkalkungen in den Arterien entfernen, oder Biologen helfen, in Zellen Strukturen zu verändern, die für eine direkte Manipulation durch die Forscher zu klein sind. In ersten Versuchen liessen die ETH-Forscher die ABFs bereits kleine Styroporkügelchen herumtransportieren. Im Moment betreibt die Gruppe allerdings noch Grundlagenforschung. Bis zu konkreten Anwendungen muss noch weiter geforscht werden. «Für Anwendungen im menschlichen Körper müssen die ABFs zunächst ganz präzise gesteuert, ihr Weg ohne optische Kontrolle verfolgt und die ABFs jederzeit lokalisiert werden können», erklärt Nelson. Wenn die ABFs Medikamente transportieren sollen, müssen sie zuerst auf geeignete Weise damit beladen werden und sie dann vor Ort gezielt wieder abgeben können. Die ABFs selber sollen noch schneller und kleiner werden. Nelson ist begeistert davon, wie genial die Natur die natürlichen Bakterien konstruiert hat. Er freut sich, dass seine Gruppe mit ihren ABFs schon so nahe an das Original herankommt. Zhang L, Abbott JJ, Dong L, Kratochvil BE, Bell D and Nelson BJ. Artificial bacterial flagella: Fabrication and magnetic control. Applied Physics Letters 94, 064107, 2009. Doi: 10.1063/1.3079655

	Stem Cells Replace Stroke-damaged Tissue In Rats ScienceDaily (Mar. 9, 2009) — Effective stem cell treatment for strokes has taken a significant step forward as scientists reveal how they have replaced stroke-damaged brain tissue in rats. The team of scientists is funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and led by Dr Mike Modo of the Institute of Psychiatry, King's College London. The work, carried out at the Institute of Psychiatry and University of Nottingham, shows that by inserting tiny scaffolding with stem cells attached, it is possible to fill a hole left by stroke damage with brand new brain tissue within 7 days. The work is published in Biomaterials on March 9. Previous experiments where stem cells have been injected into the void left by stroke damage have had some success in improving outcomes in rats. The problem is that in the damaged area there is no structural support for the stem cells and so they tend to migrate into the surrounding healthy tissues rather than filling up the hole left by the stroke. Dr Modo said: "We would expect to see a much better improvement in the outcome after a stroke if we can fully replace the lost brain tissue, and that is what we have been able to do with our technique." Using individual particles of a biodegradable polymer called PLGA that have been loaded with neural stem cells, the team of scientists have filled stroke cavities with stem cells on a ready-made support structure. Dr Modo continued: "This works really well because the stem cell-loaded PLGA particles can be injected through a very fine needle and then adopt the precise shape of the cavity. In this process the cells fill the cavity and can make connections with other cells, which helps to establish the tissue. "Over a few days we can see cells migrating along the scaffold particles and forming a primitive brain tissue that interacts with the host brain. Gradually the particles biodegrade leaving more gaps and conduits for tissue, fibres and blood vessels to move into." The research published today uses an MRI scanner to pinpoint precisely the right place to inject the scaffold-cell structure. MRI is also used to monitor the development of the new brain tissue over time. The next stage of the research will be to include a factor called VEGF with the particles. VEGF will encourage blood vessels to enter the new tissue. Professor Douglas Kell, BBSRC Chief Executive said: "Stroke is a leading cause of disability in industrialised countries. It is reassuring to know that the technology for treating stroke by repairing brain damage is getting ever closer to translation into the clinic. This crucial groundwork by Dr Modo and his colleagues will surely be a solid foundation of basic research for much better treatments in the future." Joe Korner, Director of Communications at The Stroke Association commented: "This research is another step towards using stem cell therapy in treating and reversing the brain damage caused by stroke. It is exciting because researchers have shown they are able to overcome some of the many challenges in translating the potential of using stem cells into reality. "The potential to reverse the disabling effects of stroke seems to have been proved. However the development of stem cell therapy for stroke survivors is still in the early stages and much more research will be needed before it can be tested in humans or used in practice. "Every five minutes someone in the UK has a stroke and it is vital that we do all we can to help those affected by stroke." Biotechnology and Biological Sciences Research Council (2009, March 9). Stem Cells Replace Stroke-damaged Tissue In Rats. ScienceDaily. Retrieved March 27, 2009, from http://www.sciencedaily.com /releases/2009/03/090308222732.htm

	iPS Zellen durch Plasmide mit Transposon - Durchbruch bei Stammzellenforschung? Kanadischen und britischen Forschern ist es gelungen, Hautzellen, die Erwachsenen (Maus und Mensch) entnommen wurden, zu Stammzellen in der embryonalen Form zurückzuprogrammieren - ohne den bis dato nötigen Einsatz eines Virus. Die Rückprogrammmierung von Hautzellen zu sogenannten induzierten pluripotenten Stammzellen (iPS-Zellen) könnte die regenerative Medizin verändern, schreiben die Forscher aktuell im Fachmagazin Nature (DOI:10.1038/nature07864 und DOI:10.1038/nature 07863). Die beiden Forscherteams kamen bei der Reprogrammierung der Zellen ohne die üblicherweise verwendeten Viren als Schleuser-Helfer aus, eine Technik, die die Gefahr birgt, dass die iPS-Zellen später Krebs entwickeln. Die Hoffnungen, die sich mit den Arbeiten der beiden Forschergruppen verbinden, sind groß. Zum einen würde eine erfolgreiche Reprogrammierung normaler Zellen in die pluripotenten Stammzellen bedeuten, dass die Forschung nicht mehr auf Entnahme von Stammzellen bei Embryos angewiesen wäre, eine Praxis, die sehr umstritten ist und seit Jahren von großen ethischen Diskussionen begleitet wird. Zum anderen erhofft man sich, dass Forschung eines Tages mit Alleskönnerstammzellen Krankheiten reparieren kann, die bisher unheilbar sind, wie Parkinson, Rückenmarkskrankheiten und Diabetes. Manche hoffen, dass mit Hilfe der Stammzellen irgendwann sogar Ersatzteile für beschädigte Organe gezüchtet werden könnten, die vom Körper nicht abgestoßen werden, da sie ja dieselbe DNA besitzen. Das große Hindernis: Man brauchte Viren, um die besseren Gene, die die Zelle umprogrammieren sollten, an die verschiedenen Stellen des Erbgutes zu platzieren. Die Viren, die als trojanisches Pferd fungierten, bargen jedoch die Gefahr, dass lebenswichtige Gene ausgeschaltet werden konnten, bzw. dass die Zelle zur Krebszelle entarten könnte. Zudem lieferte der Virus noch sein eigenes Erbmaterial mit. In ihren zugleich veröffentlichten Forschungspapieren stellten ein Wissenschaftsteam unter Leitung von Keisuke Kaji von der Universität von Edinburgh und ein Team aus Toronto (Mount Sinai Hospital) unter der Leitung von Andras Nagy nun neue Techniken vor, die Gensequenzen zur Umprogrammierung in die Zelle zu schleusen. Die vier dazu nötigen Gene c-Myc, Klf4, Oct4 und Sox2 wurden in einer Plasmid-Fähre in die Zelle gebracht. In dem Plasmid, einem ringförmigen DNA-Molekül, wurden die vier Gene nebeneinander eingebaut. Die kanadischen Forscher brachten zusätzlich ein springendes Gen, ein Transposon, in die Zelle. Es kann seine Lage im Erbgut verändern und damit den Einbau der vier Gene verbessern. Die sogenannte "PiggyBac"-Technik zur Einschleusung von genetischen Informationen mithilfe von Transposonen ist bereits aus der Forschung zu gentechnisch manipuliertem Getreide bekannt. Mithilfe der Transposon-Technik gelang den Forschern auch das andere große Kunststück: das Herausschneiden der vier Gene nach der Umprogrammierung. Die Zellen bleiben laut Wissenschaftler gesund und intakt, was durch Tests ebenso nachgewiesen wurde wie die Tatsache, dass sich die umprogrammierten Zellen wie Stammzellen verhielten. Davon abgesehen, dass manche Forscherkollegen bemängeln, dass man nicht genau wisse, wieviel die derart gewonnenen iPS-Zellen wert wären, ist der Weg von den Hautzellen zu den iPS-Zellen noch ziemlich aufwändig; es dürfte noch einige Zeit vergehen, bis solche Zellen für medizinische Zwecke routinemäßig herzustellen sind und für Patienten verwendet werden können, beschwichtigt Ian Wilmut, der "Vater" des Klonschafes Dolly, der an der Universität von Edinburgh tätig ist, allzu große Hoffnungen. Thomas Pany02.03.2009

	Statin use halves risk of death from prostate cancer MONDAY, Mar. 2, 2009 (HealthDay News) -- Statin use in men is independently associated with a 50 percent or greater reduced risk of death from prostate cancer, according to research presented at the American Society of Clinical Oncology's Genitourinary Cancers Symposium held Feb. 26 to 28 in Orlando. Stephen Marcella, M.D., of the UMDNJ-School of Public Health in Piscataway, N.J., and a colleague identified all New Jersey men who died from prostate cancer between 1989 and 2001, and matched each man by age and race to a population-based control. The researchers' unadjusted analysis found that statin exposure was associated with a significantly decreased risk of death from prostate cancer (odds ratio, 0.50). When they adjusted for exposure to any hypertensive medication, they found an even lower risk associated with statin exposure (odds ratio, 0.40). When they adjusted for co-morbid conditions, obesity, and education, they found that statin exposure continued to be associated with a significantly lower risk (odds ratio, 0.40). "This study adds to the body of evidence linking statin use with a decreased risk for prostate cancer death," the authors conclude.

	New Class Of Small RNAs Discovered: Function Defined ScienceDaily (Jan. 28, 2009) — Researchers at Cold Spring Harbor Laboratory (CSHL) announced today the discovery of a new class of small RNAs. At the same time, they reported that their discovery suggests the presence of a strikingly novel biochemical pathway for RNA processing in which these and possibly other small RNAs are produced. The research, which is part of a multinational project called ENCODE, also provided information concerning the biological function of the new short RNA class. The team's findings, which appeared online January 25th, ahead of print, in the journal Nature, significantly improve our understanding of how functional information is stored in the genome. The work at CSHL was spearheaded by Professors Thomas Gingeras, Ph.D., a leader of ENCODE, and Gregory Hannon, Ph.D., a world-renowned expert in small RNAs. "These results are a good illustration of why the ENCODE project was established," says Dr. Gingeras. "They show how collaborative projects can reveal functional elements and mechanisms embodied in the genome that have never before been described." Exploring vast, non-coding regions of the genome At the conclusion of the Human Genome Project in 2003, scientists published a final draft of the DNA sequence found within healthy human cells – an assemblage of roughly 3 billion "As" "Ts" "Cs" and "Gs." While justifiably proud of the feat, genome scientists knew that the most interesting part of their task was just beginning. Using the published 2003 sequence, they were able to specify across the entire genome which stretches of DNA comprised genes – regions that act as blueprints for the manufacture of proteins. To the surprise of many, those regions accounted for only about 2% of the genome. Following that realization, most of the remaining 98% began to look more like terra incognita than conquered territory. To define the full set of genomic elements that perform functions in living cells and to hunt down their location amidst the thicket of genes and non-coding DNA, a multinational project known as ENCODE (an acronym for Encyclopedia of DNA Elements) was initiated in 2003. Recent research by Professor Gingeras, who has played a major role in the project, has revealed that nearly all of the genome is converted into various types of RNA molecules, a process once thought to be restricted to protein-coding genes. What roles, if any, each of these new types of RNA play within the cell is now an important topic of research. The world of small RNAs gets bigger As one of the hubs of ENCODE, Gingeras's laboratory at CSHL is part of the effort to catalogue the entire long and short RNA output of cells. Focusing on two ENCODE- targeted human cell lines in the newly announced results, Gingeras's group, in collaboration with Hannon's laboratory, used powerful genome-sequencing techniques to zoom in on small RNA molecules and select potentially new types of RNA for further analysis. Small RNAs are one RNA subtype among several that have been discovered during the last decade. As a group, they are distinguished by the fact that they do not "code" for proteins, and are physically smaller than coding RNAs. In the small RNA group selected by the CSHL scientists for further analysis, an abundant type is one that Gingeras's group recently identified as arising specifically from transcription start sites – gene regions also known as promoters, where the synthesis of protein-coding RNA molecules begins. These promoter-associated small RNAs, or PASRs, can be contrasted with a new species just discovered by Gingeras, Hannon and colleagues, a type they call non-PASRs. The latter originate at sites distant from those where PASRs are generated. Both types of small RNAs were observed to have undergone "capping," a chemical modification that makes them stable and impervious to degradation. "This quality," Hannon observes, "lengthens their lifespan in the cell, a clue that suggests these small RNA classes may have significant biological duties." Curiously, PASRs and non-PASRs may not be initially synthesized in their "short" form. The CSHL team proposes a model in which mature long RNAs are cleaved followed by a capping of the newly generated long RNA fragment. This is followed by the clipping of the end of the capped long RNA to produce a short RNA product. Small RNAs can act as "off" switches at "on" sites Now that these new capped small RNA types have been discovered, the question naturally arises: what do they do? Using a human gene called MYC as a model, the team studied how the presence of PASRs at the start site of a gene impacted its expression, i.e., the way it manifested itself in a living cell. The researchers found that if the level of expression of PASRs was increased, the expression of the MYC gene was reduced. PASRs thus seem to modulate the production of mature RNA transcripts. The function of non-PASRs is unclear at the moment. This class of RNAs "could possibly participate more globally in a bookkeeping or quality-control mechanism by which the cell keeps track of the genes it is expressing -- its transcriptional output," according to Gingeras. This work and the future contributions of the ENCODE project have a larger significance in understanding the genetic roots of human disease. "Unless we obtain much more information about non-protein coding sequences of the genome and learn how various functional elements in the genome impact the production of proteins, we won't fully be able to understand the biological and clinical effects of disease-causing mutations," Gingeras emphasizes. Journal reference: 1. Fejes-Toth et al. Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs. Nature, January 25, 2009; DOI: 10.1038/nature07759 Adapted from materials provided by Cold Spring Harbor Laboratory, via EurekAlert!, a service of AAAS.

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