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January 07, 2011

Stem cell discovery could lead to improved bone marrow transplants and stem cells and baldness

1. Researchers at the University of California, Santa Cruz, have identified a key molecule for establishing blood stem cells in their niche within the bone marrow. The findings, reported in the January issue of Cell Stem Cell, may lead to improvements in the safety and efficiency of bone marrow transplants.


The new study shows that hematopoietic stem cells use a molecule called Robo4 to anchor themselves in the bone marrow.

"Robo4 is a rare molecule that is found only in hematopoietic stem cells and in the endothelial cells of blood vessels," said Camilla Forsberg, an assistant professor of biomolecular engineering in the Baskin School of Engineering at UC Santa Cruz. After earlier work in her lab showed that Robo4 is specific for hematopoietic stem cells, Forsberg set out to discover how it functions.

The discovery that the cells need Robo4 to stay in the bone marrow has potential therapeutic implications. An increasingly common alternative to traditional bone marrow transplants (which require anesthesia for the bone marrow extraction) involves harvesting hematopoietic stem cells from the blood. Repeated injections of drugs are needed to get the stem cells to leave the bone marrow and enter the bloodstream so that they can be collected with a blood draw. A drug that blocks Robo4 could be a safer and more effective way to do this, Forsberg said.

"If we can get specific and efficient inhibition of Robo4, we might be able to mobilize the hematopoietic stem cells to the blood more efficiently," she said. "We're already working on that in the second phase of the project."

Robo4 acts as an adhesion molecule, interacting with other components of the bone marrow to bind the stem cells into their proper niche. Forsberg's lab is trying to find out what molecules bind to Robo4, which could lead to a better understanding of that niche. While other types of stem cells are routinely grown in petri dishes, hematopoietic stem cells are very difficult to grow in the lab. They seem to require the bone marrow environment to function properly, and Forsberg's research might enable researchers to recreate that environment in a petri dish.

Other molecules besides Robo4 are also known to be involved in guiding the localization of hematopoietic stem cells in the bone marrow. Forsberg's results indicate that one of these, called Cxcr4, acts together with Robo4 to retain hematopoietic stem cells in the bone marrow. But the two molecules appear to act through different molecular mechanisms. Inhibition of both molecules may be the best way to achieve efficient mobilization of hematopoietic stem cells

2. Given the amount of angst over male pattern balding, surprisingly little is known about its cause at the cellular level. In a new study, published in the Journal of Clinical Investigation, a team led by George Cotsarelis, MD, chair of the Department of Dermatology at the University of Pennsylvania School of Medicine, has found that stem cells play an unexpected role in explaining what happens in bald scalp.

Using cell samples from men undergoing hair transplants, the team compared follicles from bald scalp and non-bald scalp, and found that bald areas had the same number of stem cells as normal scalp in the same person. However, they did find that another, more mature cell type called a progenitor cell was markedly depleted in the follicles of bald scalp.

The researchers surmised that balding may arise from a problem with stem-cell activation rather than the numbers of stem cells in follicles. In male pattern balding, hair follicles actually shrink; they don’t disappear. The hairs are essentially microscopic on the bald part of the scalp compared to other spots.

The researchers say their next steps will be to study the stem and progenitor populations in other types of hair loss, including female pattern hair loss. The information may assist in developing cell-based treatments for male pattern balding by isolating stem cells and expanding them to add back to the scalp directly. They will also focus on identifying factors that could be used topically to convert stem cells to progenitor cells to generate normal large hairs.

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