Regenerating orthopedic tissues within the human body

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By combining a synthetic scaffolding material with gene delivery techniques, researchers at Duke University are getting closer to being able to generate replacement cartilage where it’s needed in the body.Performing tissue repair with stem cells typically requires applying copious amounts of growth factor proteins — a task that is very expensive and becomes challenging once the developing material is implanted within a body. In a new study, however, Duke researchers found a way around this limitation by genetically altering the stem cells to make the necessary growth factors all on their own.They incorporated viruses used to deliver gene therapy to the stem cells into a synthetic material that serves as a template for tissue growth. The resulting material is like a computer; the scaffold provides the hardware and the virus provides the software that programs the stem cells to produce the desired tissue.The study appears online the week of Feb. 17 in the Proceedings of the National Academy of Sciences.Farshid Guilak, director of orthopaedic research at Duke University Medical Center, has spent years developing biodegradable synthetic scaffolding that mimics the mechanical properties of cartilage. One challenge he and all biomedical researchers face is getting stem cells to form cartilage within and around the scaffolding, especially after it is implanted into a living being.The traditional approach has been to introduce growth factor proteins, which signal the stem cells to differentiate into cartilage. Once the process is under way, the growing cartilage can be implanted where needed.”But a major limitation in engineering tissue replacements has been the difficulty in delivering growth factors to the stem cells once they are implanted in the body,” said Guilak, who is also a professor in Duke’s Department of Biomedical Engineering. “There’s a limited amount of growth factor that you can put into the scaffolding, and once it’s released, it’s all gone. We need a method for long-term delivery of growth factors, and that’s where the gene therapy comes in.”For ideas on how to solve this problem, Guilak turned to his colleague Charles Gersbach, an assistant professor of biomedical engineering and an expert in gene therapy. Gersbach proposed introducing new genes into the stem cells so that they produce the necessary growth factors themselves.But the conventional methods for gene therapy are complex and difficult to translate into a strategy that would be feasible as a commercial product.This type of gene therapy generally requires gathering stem cells, modifying them with a virus that transfers the new genes, culturing the resulting genetically altered stem cells until they reach a critical mass, applying them to the synthetic cartilage scaffolding and, finally, implanting it into the body.”There are a few challenges with that process, one of them being that there are way too many extra steps,” said Gersbach. “So we turned to a technique I had previously developed that affixes the viruses that deliver the new genes onto a material’s surface.”The new study uses Gersbach’s technique — dubbed biomaterial-mediated gene delivery — to induce the stem cells placed on Guilak’s synthetic cartilage scaffolding to produce growth factor proteins. …


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#Academy, #Agriculture, #Delivery, #Gene, #Pregnancy, #Proteins, #Repair, #Stem, #Study, #Tissue, #Virus

New RNA interference technique finds seven genes for head and neck cancer

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In the hunt for genetic mutations that cause cancer, there is a lot of white noise. So although genetic sequencing has identified hundreds of genetic alterations linked to tumors, it’s still an enormous challenge to figure out which ones are actually responsible for the growth and metastasis of cancer. Scientists in Rockefeller’s Laboratory of Mammalian Cell Biology and Development have created a new technique that can weed out that noise — eliminating the random bystander genes and identifying the ones that are critical for cancer. Applying their technique to head and neck cancers, they’ve discovered seven new tumor-suppressor genes whose role in cancer was previously unknown.The new technique, which the lab recently applied to a screen for skin tumor genes, is particularly useful because it takes a fraction of the resources and much less time than the traditional method for determining gene function — breeding genetically modified animals to study the impact of missing genes.”Using knockout mice, which are model organisms bred to have a particular gene missing, is not feasible when there are 800 potential head and neck cancer genes to sort through,” says Daniel Schramek, a postdoctoral fellow in the lab, which is headed by Rebecca C. Lancefield Professor Elaine Fuchs. “It can take about two years per gene. Our method can assess about 300 genes in a single mouse, in as little as five weeks.”The researchers made use of RNA interference, a natural process whereby RNA molecules inhibit gene expression. They took short pieces of RNA which are able to turn off the function of specific genes, attached them to highly concentrated viruses, and then, using ultrasound to guide the needle without damaging surrounding tissue, they injected the viruses into the sacs of mouse embryos.”The virus is absorbed and integrated into the chromosomes of the single layer of surface cells that cover the tiny embryo,” explains Fuchs. “As the embryo develops, this layer of cells becomes the skin, mammary glands and oral tissue, enabling us to efficiently, selectively and quickly eliminate the expression of any desired gene in these tissues. The non-invasive method avoids triggering a wound or inflammatory response that is typically associated with conventional methods to knockdown a gene in cultured cells and then engraft the cells onto a mouse.”When the mice grew, the researchers determined which genes, when turned off, were promoting tumor growth, and what they found was surprising.”Among the seven novel tumor suppressor genes we found, our strongest hit was Myh9, which codes for the protein myosin IIa, a motor protein with well-known function in cell structure and cell migration,” says Schramek. …


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#Biology, #Health, #Mammalian, #Mutations, #Neck, #Noise, #Protein, #Rockefeller, #Schramek, #Single, #Tumors, #Virus