Main Category: Stroke
Also Included In: Stem Cell Research; Neurology / Neuroscience
Article Date: 25 Jul 2013 – 1:00 PDT
“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,” said Jan Nolta, director of the UC Davis Institute for Regenerative Cures. “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.”
In addition to being therapeutically helpful, the Olig2PC-Astros showed no tumor formation, remained in brain areas where they were transplanted and did not differentiate into other cell types, such as neurons.
Published in the journal Nature Communications, the large, collaborative study found that astrocytes – neural cells that transport key nutrients and form the blood-brain barrier – can protect brain tissue and reduce disability due to stroke and other ischemic brain disorders.
Deng added that the therapeutic potential of astrocytes has not been investigated in this context, since making them at the purity levels necessary for stem cell therapies is challenging. In addition, the specific types of astrocytes linked with protecting and repairing brain injuries were not well understood.
The researchers then compared the effects of Olig2PC-Astros, another type of astrocyte called NPC-Astros and no treatment whatsoever on three groups of rats with ischemic brain injuries. The rats transplanted with Olig2PC-Astros experienced superior neuroprotection together with higher levels of brain-derived neurotrophic factor (BDNF), a protein associated with nerve growth and survival. The rats transplanted with NPC-Astros or that received no treatment showed much higher levels of neuronal loss.
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Stem cell study uncovers brain-protective powers of astrocytes
Additional experiments showed that both the Olig2PC-Astros and NPC-Astros accelerated synapse development in mouse neurons. The Olig2PC-Astros, however, had significantly greater protective effects over the NPC-Astros.
To determine whether the astrocytes impacted behavior, the researchers used a water maze to measure the rats’ learning and memory. In the maze, the rats were required to use memory rather than vision to reach a destination. When tested 14 days after transplantation, the rats receiving Olig2PC-Astros navigated the maze in significantly less time than the rats that received NPC-Astros or no treatment.
This research was funded in part by the NIH (grants R01NS061983, R01ES015988 and R01NS025044), National Multiple Sclerosis Society, Shriners Hospitals for Children, California Institute for Regenerative Medicine, Memorial Hermann Foundation (Staman Ogilvie Fund) and the Bentsen Stroke Center.
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University of California – Davis Health System. “Stem cell study uncovers brain-protective powers of astrocytes.” Medical News Today. MediLexicon, Intl., 25 Jul. 2013. Web.
26 Jul. 2013. <http://www.medicalnewstoday.com/releases/263861.php>
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The investigators used cell culture experiments to determine whether the astrocytes could protect neurons from oxidative stress, which plays a significant role in brain injury following stroke. They exposed neurons co-cultured with both types of astrocytes to hydrogen peroxide to replicate oxidative stress. They found that, while both types of astrocytes provided protection, the Olig2PC-Astros had greater antioxidant effects. Further investigation showed that the Olig2PC-Astros had higher levels of the protein Nrf2, which increased antioxidant activity in the mouse neurons.
Deng added that the results could lead to stem cell treatments for many neurodegenerative diseases.
The team began by using a transcription factor (a protein that turns on genes) known as Olig2 to differentiate human embryonic stem cells into astrocytes. This approach generated a previously undiscovered type of astrocyte called Olig2PC-Astros. More importantly, it produced those astrocytes at almost 100 percent purity.
“By creating a highly purified population of astrocytes and showing both their therapeutic benefits and safety, we open up the possibility of using these cells to restore brain function for conditions such as Alzheimer’s disease, epilepsy, traumatic brain disorder, cerebral palsy and spinal cord injury,” said Deng. stroke section for the latest news on this subject.