For many years, research on neurodegenerative diseases and spinal cord and brain injury has focused on damage to nerve cells, or neurons. Now, a new study of astrocytes - a type of cell that surrounds and supports neurons - finds that there is a subtype that can turn rogue and kill neurons, instead of helping to repair them during injury or disease.

The international study - conducted by a team that includes researchers from Stanford University School of Medicine in California, and the University of Melbourne in Australia - is published in the journal Nature.

The researchers suggest that the findings could lead to new treatments for brain injuries and major neurological disorders such as Alzheimer's and Parkinson's disease.

Lead author Dr. Shane Liddelow, of the department of pharmacology and therapeutics at Melbourne, and the department of neurobiology at Stanford, says that while astrocytes have often been described as "helper" cells, it has also been shown that they can become toxic and contribute to the damage caused by brain injury and disease by killing other brain cells.

"These apparently opposing effects have been a puzzle for some time. By characterizing two types of astrocytes this paper provides some answers to the puzzle," he adds.

For a long time, scientists believed that astrocytes - star-shaped cells in the central nervous system that outnumbers neurons by around five to one - were simply packing cells that provide structural support to neurons.

More recently, it has become clear that astrocytes perform a wide variety of complex and essential roles in the brain and the rest of the central nervous system.

For example, it is now known that astrocytes enhance neuron survival and help to shape brain circuitry.

It is also known that astrocytes can change from benign "resting astrocytes" into "reactive astrocytes" with altered features, following brain trauma, infection, stroke, and disease.

However, what is not so clear is whether reactive astrocytes are good or bad.

In their study paper, the team describes finding a subtype of reactive astrocytes, which they call A1, that occurs in disease and injury.

A1 astrocytes appear to lose the ability to help neurons survive and grow connections. Instead, they induce the death of neurons and oligodendrocytes, the cells that help to grow the myelin sheath that insulates connections between neurons.

In further experiments, the researchers showed that blocking A1 astrocytes stopped them killing neurons.

The researchers also found that A1 astrocytes are abundant in various human neurodegenerative diseases, including: Parkinson's disease, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis.

For example, in tissue samples from Alzheimer's patients, they found that nearly 60 percent of the astrocytes in the prefrontal cortex, a region of the brain where the disease causes the most damage, were A1 astrocytes.

Senior author Ben Barres, professor of neurobiology, developmental biology, and neurology and neurological sciences at Stanford, says that their study shows that astrocytes "aren't always the good guys," and concludes that:

"An aberrant version of them turns up in suspicious abundance in all the wrong places in brain tissue samples from patients with brain injuries and major neurological disorders from Alzheimer's and Parkinson's to multiple sclerosis. The implications for treating these diseases are profound."

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Mouse and human skin cells can be reprogrammed to hunt down tumors and deliver anticancer therapies.

Imagine cells that can move through your brain, hunting down cancer and destroying it before they themselves disappear without a trace. Scientists have just achieved that in mice, creating personalized tumor-homing cells from adult skin cells that can shrink brain tumors to 2% to 5% of their original size. Althoughthe strategy has yet to be fully tested in people, the new method could one day give doctors a quick way to develop a custom treatment for aggressive cancers like glioblastoma, which kills most human patients in 1215 months. It only took 4 days to create the tumor-homing cells for the mice.

Glioblastomas are nasty: They spread roots and tendrils of cancerous cells through the brain, making them impossible to remove surgically. They, and other cancers, also exude a chemical signal that attracts stem cellsspecialized cells that can produce multiple cell types in the body. Scientists think stem cells might detect tumors as a wound that needs healing and migrate to help fix the damage. But that gives scientists a secret weaponif they can harness stem cells natural ability to home toward tumor cells, the stem cells could be manipulated to deliver cancer-killing drugs precisely where they are needed.

Other research has already exploited this methodusing neural stem cellswhich give rise to neurons and other brain cellsto hunt down brain cancer in mice and deliver tumor-eradicating drugs. But few have tried this in people, in part because getting those neural stem cells is hard, says Shawn Hingtgen, a stem cell biologist at the University of North Carolina inChapel Hill. Right now, there are three main ways. Scientists can either harvest the cells directly from the patient, harvest them from another patient, or they can genetically reprogram adult cells. But harvesting requires invasive surgery, and bestowing stem cell properties on adult cells takes a two-step process that can increase the risk of the final cells becoming cancerous. And using cells from someone other than the cancer patient being treated might trigger an immune response against the foreign cells.

To solve these problems, Hingtgens group wanted to see whetherthey could skip a step in the genetic reprogramming process, which first transforms adult skin cells into standard stem cells and then turns those into neural stem cells. Treating the skin cells with a biochemical cocktail to promote neural stem cell characteristics seemed to do the trick, turning it into a one-step process, he and his colleague report today in Science Translational Medicine.

But the next big question was whether these cells could home in on tumors in lab dishes, and in animals, like neural stem cells. We were really holding our breath, Hingtgen says. The day we saw the cells crawling across the [Petri] dish toward the tumors, we knew we had something special. The tumor-homing cells moved 500 micronsthe same width as five human hairsin 22 hours, and they could burrow into lab-grown glioblastomas. This is a great start, says Frank Marini, a cancer biologist at the Wake Forest Institute forRegenerative Medicine in Winston-Salem, North Carolina,who was not involved with the study. Incredibly quick and relatively efficient.

The team also engineered the cells to deliver common cancer treatments to glioblastomas in mice. Mouse tumors injected directly with the reprogrammed stem cells shrank 20- to 50-fold in 2428 days compared withnontreated mice. In addition, the survival times of treated rodents nearly doubled. In some mice, the scientists removed tumors after they were established, and injected treatment cells into the cavity. Residual tumors, spawned from the remaining cancer cells, were 3.5 times smaller in the treated mice than in untreated mice.

Marini notes that more rigorous testing is needed to demonstrate just how far the tumor-targeting cells can migrate. In a human brain, the cells would need to travel a matter of millimeters or centimeters, up to 20 times farther than the 500 microns tested here, he says. And other researchers question the need to use cells from the patients own skin. An immune response, triggered by foreign neural stem cells, could actually help attack tumors, says Evan Snyder, a stem cell biologist at Sanford Burnham Prebys Medical Discovery Institute in San Diego, California, and one of the early pioneers of the idea of using stem cells to attack tumors.

Hingtgens group is already testing how far their tumor-homing cells can migrate using larger animal models. They are also getting skin cells from glioblastoma patients to make sure the new method works for the people they hope to help, he says. Everything were doing is to get this to the patient as quickly as we can.

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Reprogrammed skin cells shrink brain tumors in mice | Science | AAAS - Science Magazine