Working to Bend Stem Cells to Our Will

Scientists the world over are working hard to control stem cells - because if you can control stem cells, if you understand the biochemical cues and pathways in charge of their biomolecular machinery, you can regrow and regenerate pretty much any portion of the body you care to, as well as potentially turn off all cancers ... and those are just two of many uses for such a capability. Here are a couple of recent items from the popular science press illustrative of present work:

Liposuctioned fat stem cells to repair bodies:

Expanding waistlines, unsightly bulges: people will gladly remove excess body fat to improve their looks. But unwanted fat also contains stem cells with the potential to repair defects and heal injuries in the body. A team led by Philippe Collas at the University of Oslo in Norway has identified certain chemical marks that allow him to predict which, among the hundreds of millions of stem cells in liposuctioned fat, are best at regenerating tissue.

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That fat-based methods work is not surprising, perhaps, because adipose tissue is closely related to bone, cartilage, muscle and other connective tissue. But some say it is impossible to re-programme adult cells to become nerve or liver cells, for example, without using embryos. Adult stem cells, such as those from fat, are thought to have more limited potential.

Collas insists that the transformation is possible. The hurdle lies not with the genes but with a cell’s epigenetic status, the subtle chemical modifications of DNA and its surrounding histone proteins. Epigenetic marks contribute to switching genes on and off, and stem cells rely on them heavily as they divide and mature. The Oslo team has found that low rates of DNA methylation, for instance, boost the chances of transforming fat stem cells from one cell type into another. "Look at a cell’s epigenetic profile," says Collas, "and you may be able to predict what that cell is likely to turn into."

How stem cells are regulated:

Director of BRIC, Professor Kristian Helin led the research team consisting of Jesper Christensen, Karl Agger and Paul Cloos. Last year, the same research group published an article in Nature on how a group of Jumonji proteins regulate the growth of cancer cells and are involved in the development of specific cancer types.

BRIC’s new results show that a different subgroup of Jumonji proteins is essential for cellular differentiation. The Jumonji enzymes can turn off, or inactivate, particular genes that play an important part in embryogenesis. The conclusions are based on studies of the nematode (roundworm) C. elegans and studies of mouse embryonic stem cells. The C. elegans studies were carried out in collaboration with another of BRIC’s research groups, led by Associate Professor Lisa Salcini.

The BRIC researchers are currently developing inhibitors to the Jumonji proteins. Their aim is to use these inhibitors to treat cancer patients with increased levels of the Jumonji proteins.

Scientists produce neurons from human skin:

Tests conducted by the researchers demonstrated that stem cells from the skin can proliferate and differentiate in vitro when placed in the appropriate environment. They progressively took on the oblong shape typical of neurons. At the biochemical level, researchers discovered that in the days following the start of the experiment, the cells began producing markers and molecules associated with the transmission of nerve impulse between neurons. "This suggests the beginning of synapse formation between neurons," points out Professor Berthod.

In the short term, this breakthrough might have an impact in the field of neuroscience research. "Producing neurons from skin cells could solve the problem of human neural cell availability for research," explains Berthod. "Since neurons do not multiply, researchers now have to rely on laboratory animal neurons to perform their experiments."

In the longer term, the ability to produce neurons from skin cells opens the door to revolutionary therapeutic applications. "We could take a patient’s skin cells and use them to produce perfectly compatible neurons, thus eliminating the risk of rejection. We could then transplant these nerve cells in the diseased areas of the brain," explains Berthod. "This type of procedure seems particularly interesting for diseases such as Parkinson’s, but it’s all theoretical for now. Before we can think of doing such things, we’ll have to improve nerve cell differentiation and prove that they can transmit nerve impulses," concludes the researcher.

Take a few minutes one of these days to stroll back a few years in the archives of one of the popular science websites - you'll be impressed at how fast the basic science is moving in this field.

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