“Latest Stem Cells News”

Scientists have developed a new tool that illuminates connections between stem cells and cancer.
Researchers have been successful in breaking apart human prostate tissue, extract the stem cells in the tissue, and alter those cells genetically so that they spur cancer.

Many tissues contain pools of stem cells that replenish the tissue when it’s damaged or when changes take place. For example, stem cells in the skin produce new cells to replace those irreparably damaged by the sun, and stem cells in the breast create milk-producing cells when a woman is pregnant.

A characteristic of these stem cells is that they self-renew. This means that in addition to making cells with a specific function, they also make many new stem cells.

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Never mind facial masks and exfoliating scrubs, skin takes care of itself. Stem cells located within the skin actively generate differentiating cells that can ultimately form either the body surface or the hairs that emanate from it. In addition, these stem cells are able to replenish themselves, continually rejuvenating skin and hair. Now, researchers at Rockefeller University have identified two proteins that enable these skin stem cells to undertake this continuous process of self-renewal.

The work, published in Nature Genetics, brings new details to the understanding of how stem cells maintain — and lose — their status as stem cells and are able to specialize into various types of cells. It also further dissects a ubiquitous Rube Goldberg-like pathway whose molecular gears and levers play an important role in activating stem cells to divide and transform into tissue-making cells.

Lead researcher Elaine Fuchs, head of the Laboratory of Mammalian Cell Biology and Development, and first author Hoang Nguyen, a former postdoc in the lab, worked with mice engineered to lack the proteins TCF3 and TCF4, which reside in the nucleus of skin stem cells, where they bind to DNA to turn genes off that would otherwise cause the stem cells to differentiate. They found that without TCF3 and TCF4, all of the layers of the mice’s skin still develop properly, but they cannot be maintained.

“The epidermal stem cells — one of the types of stem cells in the skin — lose their capacity to self-renew and replace skin cells that have died,” says Nguyen, who is now an assistant (…)

from http://www.sciencedaily.com/releases/2009/09/090927152828.htm

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The addition of two particular gene snippets to a skin cell’s usual genetic material is enough to turn that cell into a fully functional neuron, report researchers from the Stanford University School of Medicine. The finding, published online July 13 in Nature, is one of just a few recent reports of ways to create human neurons in a lab dish.

The new capability to essentially grow neurons from scratch is a big step for neuroscience research, which has been stymied by the lack of human neurons for study. Unlike skin cells or blood cells, neurons are not something that’s easy for a living human to donate for research.

“A major problem in neurobiology has been the lack of a good human model,” said senior author Gerald Crabtree, MD, professor of pathology and of developmental biology. “Neurons aren’t like blood. They’re not something people want to give up.”

Generating neurons from easily accessible cells, such as skin cells, makes possible new ways to study neuronal development, model disease processes and test treatments.

It also helps advance the effort, still in its infancy, to replace damaged or dead neurons with new ones.

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Using two distinct methods, Whitehead Institute researchers have successfully and consistently manipulated targeted genes in both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells (adult cells that have been reprogrammed to an embryonic stem cell-like state).

In one case, scientists employed proteins known as zinc finger nucleases (ZFNs) to change a single base pair in the genome, allowing them either to insert or remove mutations known to cause early-onset Parkinson’s disease (PD). The second method relies on proteins called transcription activator like effector nucleases (TALENs) capable of altering specific genes with similar efficiency and precision as ZFNs. Both sets of experiments were conducted in close collaboration with scientists at Sangamo BioSciences.

Targeted genetic manipulation addresses a problem that has been plaguing human stem cell research – the ability to cleanly and site-specifically modify the genomes of human ES and iPS cells. Realizing the therapeutic promise of these cells depends on such changes to fix disease-causing mutations before the cells could be transplanted into patients or to create cell lines that researchers can use to study genetic diseases.

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An innovative experimental treatment for boosting the effectiveness of blood stem-cell transplants with umbilical cord blood has a favorable safety profile in long-term animal studies, according to Harvard Stem Cell Institute (HSCI) scientists at Dana-Farber Cancer Institute (DFCI), Beth Israel Deaconess Medical Center (BIDMC), and Children’s Hospital Boston (CHB).

Analysis of long-term safety testing in nonhuman primates, published online by the journal Cell Stem Cell in a new section called “Clinical Progress,” revealed that a year following transplant umbilical cord blood units treated with a signaling molecule called 16,16-dimethyl PGE2 reconstituted all the normal types of blood cells, and none of the animals receiving treated cord blood units developed cancer. Wolfram Goessling is the first author of the paper; his HSCI colleague Trista North is the senior author.

The results of long-term safety studies in mice were previously submitted to the Food and Drug Administration to gain permission for a Phase I clinical trial under an investigational new drug (IND) application. Principal investigator Corey Cutler, a Dana-Farber transplant specialist, initiated the trial in 2009 at Dana-Farber and Massachusetts General Hospital. The IND is sponsored by Fate Therapeutics Inc. of San Diego.

Goessling and North were postdoctoral fellows in the laboratory of co-author Leonard Zon, a stem cell researcher at CHB and a scientific founder of Fate Therapeutics, when they hit upon 16,16-dimethyl PGE2 while looking for compounds that could regulate the production of hematopoietic stem cells (blood stem cells). The initial testing made use of zebrafish models.

“This is the first time a compound discovered in zebrafish has received a nod from the FDA for a clinical trial,” said Goessling.

One of the limitations of cord blood as a transplant source is that the cells engraft, or “take,” in the recipient’s bone marrow more slowly than matched donor cells form bone marrow. In addition, there is a higher failure rate for cord blood transplants. Thus there is a need for ways to improve the speed and quality of cord blood transplantation.

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Howard Hughes Medical Institute (HHMI) scientists have discovered that endothelial cells, the building blocks of the vascular system, keep blood stem cells dividing healthily in a lab dish much longer and more effectively than previous methods of growing the cells. The new advance dramatically improves scientists’ ability to manufacture large quantities of authentic adult blood stem cells, which may help revolutionize the field of bone marrow transplantation.

Shahin Rafii, an HHMI investigator at Weill Cornell Medical College in New York City, and his colleagues report on the development of an endothelial cell platform that supports self-renewal of the blood stem cells, known as long-term hematopoietic stem cells (LT-HSCs), in the March 2010 issue of the journal Cell Stem Cell. Their study also describes a novel mechanism by which endothelial cells support propagation of LT-HSCs in adult mice.

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