Tag Archive for 'Cell biology'

Blood Vessel Cells Are Key to Growing Unlimited Amounts of Adult Stem Cells

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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MyoD Helps Stem Cells Proliferate in Response to Muscle Injury

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The master regulator of muscle differentiation, MyoD, functions early in myogenesis to help stem cells proliferate in response to muscle injury, according to researchers at Case Western Reserve University.
The study appears online Jan. 4 in the Journal of Cell Biology.

STEM CELLS BATTLE FOR SPACE

The body is a battle zone. Cells constantly compete with one another for space and dominance. Though the manner in which some cells win this competition is well known to be the survival of the fittest, how stem cells duke it out for space and survival is not as clear. A study on fruit flies published in the October 2 issue of Science by Johns Hopkins researchers describes how stem cells win this battle by literally sticking around.

“Our work exemplifies how one signal coordinately maintains two types of stem cells in a single niche, or microenvironment,” says Erika Matunis, Ph.D., associate professor of cell biology at the Johns Hopkins School of Medicine. “What we found may emerge as common themes of mammalian stem cell niches as they become better characterized.”

To tackle the stem cell competition quandary, the team looked at fruit fly testes where two different stem cells exist: germline stem cells which give rise to sperm, and somatic stem cells which develop into non-reproductive cell types.

Using genetics, the researchers grew flies lacking the SOCS protein, which controls other molecules that promote stem cell growth. SOCS normally ensures that the right numbers of stem cells are present in the stem cell niche, a region at the far end of the fly testis where new cells are born. In a normal testis, the germline stem cells are surrounded by somatic stem cells at a ratio of about one germline stem cell for every two somatic stem cells.

The researchers isolated testes from flies lacking SOCS and, under a microscope, counted the number of germline stem cells and somatic stem cells. They found that nearly half of the germline stem cells were gone and the somatic stem cells appeared to be occupying that space.

“The somatic stem cells almost look like they’ve invaded the niche area,” says Melanie Issigonis, a graduate student in the Biochemistry, Cellular, and Molecular Biology graduate program at Johns Hopkins. “I saw that image and said, ‘Wow, it’s right there. Germline stem cell loss.’”

To figure out where the lost germline stem cells went and how they lost the battle for space, the team returned to the microscope. This time, they examined the cells for whether they contained integrin, a protein that helps cells stick to each other. They found that somatic stem cells from flies lacking SOCS seemed to contain more integrin than somatic stem cells from flies with functional SOCS. According to Matunis, it’s the increase in integrin that allows somatic stem cells to gain the upper hand because they can stick to the niche better than neighboring germline stem cells can.

Though the somatic stem cells were invading the niche, germline stem cells were not dying. In the microscope images, the team found that all remaining germline stem cells still looked alive and healthy, but elbowed out of their niche by somatic stem cells. Says Matunis, no matter how healthy a germline stem cell is, if it cannot stick, it will eventually be outcompeted by the somatic cells and pushed all the way out of the niche. Issigonis found the discovery remarkable: “The germline stem cells are perfectly fine,” she says. “They’re just leaving the niche and differentiating.”

The team believes this model can be applied to other stem cell niches such as cancer. Just like the somatic stem cells overrunning the fly testes, cancer stem cells in mammalian systems become a danger when they become the stickiest cell in the niche. In both cases, the important control protein, SOCS, is lost. Knowing what is necessary for some stem cells to thrive and others to dwindle could have great importance to understanding the roots of stem cell diseases.

from http://www.hopkinsmedicine.org/Press_releases/2009/12_04a_09.html

Umbilical Stem Cells May Help Recover Lost Vision for Those With Corneal Disease

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CINCINNATI—New research from the University of Cincinnati may help in the recovery of lost vision for patients with corneal scarring.

Winston Whei-Yang Kao, PhD, professor of ophthalmology, along with other researchers in UC’s ophthalmology department found that transplanting human umbilical mesenchymal stem cells into mouse models that lack the protein lumican restored the transparency of cloudy and thin corneas.

Mesenchymal stem cells are “multi-potent” stem cells that can differentiate into a variety of cell types.

These findings are being presented Dec. 8 in San Diego at the 49th Annual Meeting of the American Society of Cell Biology.

“Corneal transplantation is currently the only true cure for restoration of eyesight that may have been lost due to corneal scarring caused by infection, mechanical and chemical wounds and congenital defects of genetic mutations,” Kao says. “However, the number of donated corneas suitable for transplantation is decreasing as the number of individuals receiving refractive surgeries, like LASIK, increases.”

“Worldwide, there is a shortage of suitable corneas for transplantation, and at the present time, there is no effective alternative procedure besides corneal transplantation to treat corneal blindness,” he continues. “There is a large need to develop alternative treatment regimens, one of which may be the transplantation of mesenchymal stem cells.”

Researchers used mouse models that did not have the lumican gene, also known as lumican knock-out models. Lumican is a protein that controls the formation and maintenance of transparent corneas.

“Lumican knock-out models manifested thin and cloudy corneas,” he says. “Transplantation of the umbilical stem cells significantly improved transparency and increased corneal stromal thickness in these mice.”

In addition, Kao says, the umbilical mesenchymal stem cells survived in the mouse stroma (connective tissue) for more than three months with minimal or no rejection and became corneal cells, repairing lost functions caused by mutations.

“Our results suggest a potential treatment regimen for congenital and/or acquired corneal diseases,” he says, adding that the availability of human umbilical stem cells is almost unlimited. “These stem cells are easy to isolate and can be recovered quickly from storage when treating patients.

“These findings have the potential to create new and better treatments—and an improved quality of life—for patients with vision loss due to corneal injury.”

This study was funded by grants from the National Eye Institute, Research to Prevent Blindness and the Ohio Lions Eye Research Foundation.

from http://healthnews.uc.edu/news/?/9613/

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Stem Cell Review: Tools for Drug Screening

Researchers and using stem cells as tools for disease study, drug screening, clinical trial strategy, and personalized medicine. The induced Pluripotent Stem cell (iPS) is giving us a chance to rethink the way we are developing new drugs. These iPS cells are usually created from somatic cells (such as skin), and not embryos or adult stem cells. In creating iPS from patients’ diseased cells, scientists can study the disease in vitro, looking for disease phenotypes, applying microenvironmental stress, and testing new drugs. Compared to animal model testing (e.g. mice), this represents a significant breakthrough, that can be used to validate clinical development strategy and test efficacy in specific groups of patients. iPS is bringing a revolution in drug discovery methodology which is being used to bridge genetics, cell biology, and physiology.

from http://biobusiness.tv/videos/208

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Two Proteins let Skin Cells to return to life

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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