Stem cell researchers have discovered that astrocytes may prove useful against stroke and other brain disorders.
Astrocytes - neural cells that form the blood-brain barrier and so control what can and cannot enter the brain from the blood supply - have previously been overlooked in this area of stroke research.
A collaborative study published in Nature Communications suggests that astrocytes can do far more than simply support nerve cells (neurons).
Wenbin Deng, senior author of the study and associate professor of biochemistry and molecular medicine at UC Davis in California, told Medical News Today:
"This exciting research uncovers the brain-protective powers of stem cell-derived astrocytes.
Astrocytes may help to limit the spread of damage after an ischemic brain stroke in patients, and may also help to regenerate and repair damaged brain cells.
Both of these actions may lead to better functional recovery in patients."
Dr. Wenbin Deng added that astrocyte-centered therapy "could also be used for many other nervous system disorders." He said the following could be included in a list of potential targets for therapy:
- Traumatic brain injury
- Cerebral palsy
- Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease
- Spinal cord injury.
Stem cell research has focused until now on developing stroke treatments using therapeutic neurons to stimulate electrical impulses in the brain, and restore tissue that has been damaged by oxygen deprivation. Dr. Wenbin Deng said astrocytes had often been considered just "housekeeping" cells that merely support nerve cells.
An astrocyte - more useful than previously thought. Courtesy Dr. Peng Jiang
"But they're actually much more sophisticated," Dr. Wenbin Deng explained. "They are critical to several brain functions and are believed to protect neurons from injury and death. They are not excitable cells like neurons and are easier to harness. We wanted to explore their potential in treating neurological disorders, beginning with stroke."
The UC Davis team faced an immediate challenge, however - there was little existing understanding on which specific types of astrocyte might have therapeutic potential in brain disorders. Also, the principal reason astrocytes had not been investigated in this context was the difficulty in producing them to the purity levels needed for stem cell therapies.
'Surprising twist of fate'
The UC Davis team decided to use a transcription factor protein called Olig2 to differentiate human embryonic stem cells into astrocytes. This approach generated a previously undiscovered type of astrocyte called Olig2PC-Astros - it was almost 100% pure.
"In this study, we report a surprising twist of fate," Dr. Wenbin Deng told MNT. He added:
"Our novel findings are that highly purified Olig2+ progenitors can give rise to astrocytes and that these astrocytes derived from highly purified Olig2+ progenitors are different from the astrocytes described in any previous work."
In short, the team's quest for a sufficiently pure astrocyte had, by serendipity, also led them to isolate a previously unknown astrocyte with particularly therapeutic properties.
How astrocyte effects were measured
Researchers used three groups of rats with ischemic brain injuries to compare the effects of Olig2PC-Astros, another type of astrocyte called NPC-Astros, and no treatment. The animals were placed in a water maze to assess their learning and memory.
Two weeks after transplantation, the rats receiving Olig2PC-Astros navigated the maze significantly quicker than the other groups. This group also exhibited higher levels of brain-derived neurotrophic factor (BDNF), a protein associated with nerve growth and resilience.
Cell cultures were also used to measure what protection the astrocytes could provide to neurons against the oxidative stress that contributes to brain injury following stroke.
When exposed to hydrogen peroxide, both types of astrocytes provided some protection but the Olig2PC-Astros showed greater antioxidant effects. Further investigation indicated higher levels of the protein Nrf2, which increases antioxidant activity in mouse neurons.
Additionally, the Olig2PC-Astros cells remained in brain areas where they were transplanted, did not differentiate into neurons or other cell types and formed no tumors.
Jan Nolta, director of the UC Davis Institute for Regenerative Cures, commented: "Dr. Deng's team has shown that this new method for deriving astrocytes from embryonic stem cells creates a cell population that is more pure and functionally superior to the standard method for astrocyte derivation."
Jan Nolta added:
"The functional improvement seen in the brain injury models is impressive, as are the higher levels of BDNF.
I will be excited to see this work extended to other brain disease models such as Huntington's disease and others, where it is known that BDNF has a positive effect."