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April 2nd, 2009 San Antonio STGEC Geriatrics Gerontological + Palliative Medicine Grand Rounds re: "Stem Cell-Based Therapy: Potential for Age-Related Dise...

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Newswise DALLAS March 9, 2014 For the first time, researchers have shown that an essential biological process known as protein synthesis can be studied in adult stem cells something scientists have long struggled to accomplish. The groundbreaking findings from the Childrens Medical Center Research Institute at UTSouthwestern (CRI) also demonstrate that the precise amount of protein produced by blood-forming stem cells is crucial to their function.

The discovery, published online today in Nature, measures protein production, a process known as translation, and shows that protein synthesis is not only fundamental to how stem cells are regulated, but also is critical to their regenerative potential.

We unveiled new areas of cellular biology that no one has seen before, said Dr. Sean Morrison, Director of the Childrens Research Institute, Professor of Pediatrics, and the Mary McDermott Cook Chair in Pediatric Genetics at UTSouthwestern Medical Center. No one has ever studied protein synthesis in somatic stem cells. This finding not only tells us something new about stem cell regulation, but opens up the ability to study differences in protein synthesis between many kinds of cells in the body. We believe there is an undiscovered world of biology that allows different kinds of cells to synthesize protein at different rates and in different ways, and that those differences are important for cellular survival.

Dr. Adrian Salics laboratory at Harvard Medical School chemically modified the antibiotic puromycin in a way that made it possible to visualize and quantify the amount of protein synthesized by individual cells within the body. Dr. Robert A.J. Signer, a postdoctoral research fellow in Dr. Morrisons laboratory and first author of the study, realized that this reagent could be adapted to measure new protein synthesis by stem cells and other cells in the blood-forming system.

What they came across was astonishing, Dr. Morrison said. The findings suggested that different types of blood cells produce vastly different amounts of protein per hour, and stem cells in particular synthesize much less protein than any other blood-forming cells.

This result suggests that blood-forming stem cells require a lower rate of protein synthesis as compared to other blood-forming cells, said Dr. Morrison, the papers senior author.

Researchers applied the findings to a mouse model with a genetic mutation in a component of the ribosome the machinery that makes proteins and the rate of protein production was reduced in stem cells by 30 percent. The scientists also increased the rate of protein synthesis by deleting the tumor suppressor gene Pten in blood-forming stem cells. In both instances, stem cell function was noticeably impaired.

Together, these observations demonstrate that blood-forming stem cells require a highly regulated rate of protein synthesis, such that increases or decreases in that rate impair stem cell function.

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Stem Cell Study Opens Door to Undiscovered World of Biology

Scientists from the Harvard School of Engineering and Applied Sciences (SEAS) have developed a new gel-based material that could allow stem cells to fill in the gaps in teeth and bones. This advance in tissue engineering comes from an examination of embryonic development. The researchers have essentially created a material that mimics the physical conditions under which tissue forms naturally specifically, the gel shrinks.

Tissue engineers have been wrestling with the difficulties of coaxing human cells to form three-dimensional structures in the lab, but the combination of growth factors and artificial gene activation cant quite get us there. The bio-inspired gel developed at SEAS could be the first step in solving those problems. This is the first approach that has taken a process called mesenchymal condensation into account.

Mesenchymal condensation is a process involving two tissue layers in embryos where organ formation takes place. A layer of undifferentiated connective tissue cells (mesenchyme) and an epithelium exchange biochemical signals, which causes the mesenchymal cells to contract and form a small knot right where the new organ tissue is supposed to develop (see the image at the top). Mesenchymal cells are a type of stem cell that can develop into bone, enamel, fat, and other mature cells.

The gel developed at SEAS simulates the compressionthat mesenchymal cells would experience naturally in mesenchymal condensation. A modified form of PNIPAAm polymer forms the base of the gel. It normally contracts when warmed slightly, but was tweaked in this experiment to activate at body temperature. The loose matrix of the gel is impregnated with mesenchymal cells, which are compressed as it warms. Thats how theyre encouraged to start differentiating into the appropriate types of cells and lay down new tissues, in this case teeth composed of dentin and enamel.

In embryonic development, mesenchymal cells cant form complete teeth without that extra epithelial layer. The team hopes to test its shrinking gel with both tissue layers to see if it can form a full tooth all on its own. Other tissue types could follow if the team finds that its shrinking gel works.

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New shrinking gel could help repair damaged teeth or bones