Scientists have developed a therapeutic technique using stem cells in mice with stroke-induced brain damage that dramatically increases the production of nerve cells. The study was funded by National Institutes of Health (NIH) and was published in Nature Medicine.
The team of researchers combined two kinds of treatments to optimize results, according to the NIH article. The first was to surgically graft neural stem cells on injured neural cells so that they mature to neurons and brain cells. The second was giving the mice a compound called 3K3A-APC, which has been shown to help neural stem cells grow into neurons in a petri dish. This study looked at the effect the molecule would have in live animals.
The mice who had received stem cells and 3K3A-APC performed much better on motor and sensory tests about one month later. The stem cells developed into neurons more often in the mice who received 3K3A-APC, too.
“This USC-led animal study could pave the way for a potential breakthrough in how we treat people who have experienced a stroke,” added Jim Koenig, Ph.D., a program director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which funded the research, in the NIH article. “If the therapy works in humans, it could markedly accelerate the recovery of these patients.”
Each year, about 795,000 people will suffer from a stroke. This condition leaves many people disabled. This research has the potential to help these people.
Researchers induced stroke-like brain damage by reducing blood supply to one part of the brain in mice. Then one week later, the equivalent to several months in humans, researchers inserted stem cells next to dead tissue, and the mice were given either 3K3A-APC or a placebo.
“When you give these mice 3K3A-APC, it works much better than stem cells alone,” said Berislav Zlokovic, M.D., Ph.D., the University of Southern California professor who led the research, in the NIH article. “We showed that 3K3A-APC helps the cells convert into neurons and make structural and functional connections with the host’s nervous system.”
Research out of Stanford showed that stem cells were a safe, effective treatment for strokes, but they did not use the 3K3A-APC molecule. It’s possible that this combination treatment could be even more effective.
The researchers were tasked with proving that the stem cells were responsible for the improved functioning. They gave a second group of mice who received the combination treatment a toxin that would kill the neurons that developed from the stem cells. The improvements were present before they were given the toxin, but the benefits disappeared after the toxin was given, proving the neurons that developed from the stem cells were responsible for the improvement.
The researchers performed a separate experiment to test the connections between the neurons that grew from stem cells in the damaged part of the brain and an area of the brain called the primary motor cortex. The mice given stem cells and 3K3A-APC had many more connections, called synapses, between these two areas of the brain than the placebo group. Also, when the researchers stimulated the mouse’s paw with a vibration, the neurons that developed from stem cells responded much more strongly in the treated group.
“That means the transplanted cells are being functionally integrated into the host’s brain after treatment with 3K3A-APC,” Dr. Zlokovic said in the NIH article. “No one in the stroke field has ever shown this, so I believe this is going to be the gold standard for future studies.”
The researchers hope to do a Phase-II clinical trial that explores the combination treatment of stem cells and 3K3A-APC in human stroke patients. If this trial is successful, they could start to explore this treatment in other neurological conditions, such as spinal cord injuries, for which stem cell treatments are being investigated.
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