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UC Davis researchers discover new source of brain cells

Neuron © iStockphoto
UC Davis researchers have found that neural progenitor cells are present throughout the brain and spinal cord and can differentiate into neurons.

Discovery could speed progress on stem cell treatments of brain disorders

Twenty-six years after scientists first suspected their existence, UC Davis researchers provide definitive evidence that certain neural progenitor cells, which can be identified by their expression of a myelin gene promoter, are present throughout the adult brain and spinal cord, and that these cells are capable of differentiating into neurons.

“Neural progenitor cells have the capacity to self-renew and to form many types of nerve cells,” said David Pleasure, director of the UC Davis Institute for Pediatric Regenerative Medicine.

Using genetic fate mapping — a technique for detailing the developmental path of cells — Pleasure and his team found that cells known as PPEPs (pronounced pee-peps) differentiate into the three main types of neural cells: astrocytes, oligodendrocytes and neurons. Neurons are the main cells of the brain, responsible for communicating with each other and responding to stimuli. The other two cell types — known as glial cells — play supporting roles in brain functions.

“After all these years, we can really start calling PPEPs stem cells,” said Pleasure, also a UC Davis professor of neurology.

The findings, reported in June 2009 issue of the Journal of Neuroscience, open up a new way of thinking about using multipotent progenitor cells to treat diseases of the brain and spinal cord, such as Huntington’s disease and traumatic brain injury. Now the UC Davis team and other stem cell scientists have a new class of endogenous neural progenitor cells with which to work.

Dr. Pleasure © 2009 UC Regents“I think our findings are really going to open up the field that eventually could lead to new and better treatments for patients.”
— David Pleasure

Previously, multipotent progenitor cells were only found in specialized regions of the brain, such as those that migrate to the olfactory bulb, which is responsible for smell recognition. Because PPEPs are evenly distributed throughout the central nervous system, treatments could be developed that prompt them to differentiate and repair or replace nearby central nervous system cells. This could eliminate the need for transplanting stem cells, either from the same person or from another, to sites of damage or disease.

“This is a very important progenitor cell population in the central nervous system and I think our findings are really going to open up the field that eventually could lead to new and better treatments for patients,” Pleasure said.

UC Davis Stem Cell Program

Artist version of new stem cell research building © 2009 UC Regents

UC Davis is taking a leading role in stem cell research, with more than 135 scientists and physicians currently working on a variety of stem cell investigations.

The university is finishing up construction on its Institute for Regenerative Cures, a facility supported by the California Institute for Regenerative Medicine.

The 90,000 square-foot research facility is located in Sacramento and will enable researchers to have access to state-of-the-art laboratories and cell manufacturing and testing rooms.

For more information, visit their Web site.

PPEPs are a subset of cells called NG2 progenitors. Scientists reported nearly three decades ago that they were able to coax NG2 progenitors into differentiating into astrocytes and oligodendrocytes in tissue cultures. These results, however, could not be duplicated in vivo, meaning that the cells could not be found in live animals.

“This led most investigators to decide the observations were a tissue-culture artifact,” explained Fuzheng Guo, the study’s first author and a postdoctoral fellow in Pleasure’s lab.

In the 1990s, researchers using modern techniques to replicate the original tissue-culture results found PPEPs in a few areas of the brain and provided the first tissue-culture evidence that the cells could be coaxed into differentiating into neurons. In the current study, the UC Davis team used fate-mapping to show that PPEPs can differentiate into neurons, astroglia and oligodendrocytes in live animals. They conducted an exhaustive anatomical study, looking at more areas of the central nervous system than previous researchers. Starting with seven-day-old mice with permanently labeled PPEP cells, the team found that when they later looked at the grown animals, all three cell types were labeled with the appropriate protein.

“The cells that came from the PPEPs were fully functional,” Guo said. “Our paper provides definitive evidence that these cells exist in vivo. Now, there no longer is any question about this issue.”

The findings are among many exciting recent discoveries for stem cell researchers, Pleasure said. In the last 10 years, for instance, scientists have dispelled the myth that humans do not create new neurons after birth.

“People have talked about transplanting from these niches, but these are small, specific areas of the brain,” explained Joyce Ma, a medical student and Ph.D. candidate who is also one of the study authors working in Pleasure’s lab. “The beauty of PPEPs is that they are scattered throughout the brain and spinal cord. If we can understand what controls their proliferation and differentiation we may be able to prod them into treating disease.”

Joyce Ma © 2009 UC Regents
On the front page: Ph.D. candidate and medical student Joyce Ma, one of the study authors.

Working toward that understanding is what Pleasure and his team will be doing next.

Additional authors of the current study were Erica McCauley and associate project scientist Peter Bannerman.

The research was supported by grants from the National Institutes of Health, the National Multiple Sclerosis Society, a pre-doctoral fellowship from the California Institute for Regenerative Medicine and a postdoctoral fellowship from the Shriner’s Hospitals for Children.