A team of researchers has developed a therapeutic technique that dramatically increases the production of nerve cells in mice with stroke-induced brain damage. The therapy uses a compound called 3K3A-APC.
A woman having brain stroke


This is astonishing news for the people who are suffering from neurological diseases or having brain stroke. Generally when a people have a stroke blood flow into the brain is interrupted, causing brain cells to die within minutes because of lack of oxygen. In some cases, this can result in paralysis, speech and language problems, vision problems, and memory loss. But in a new study, researcher shave shown that stem cell therapy increases nerve cell production in mice with brain damage due to stroke.

Researchers and clinicians have long hope of helping the injured brain repair itself by creating new neurons, and an innovative NIH-funded study published today in Nature Medicine may bring this goal much closer to reality. A team of researchers has developed a therapeutic technique that dramatically increases the production of nerve cells in mice with stroke-induced brain damage.

Types of brain stroke. These stroke is due to blood leaks and blood colts stop the flow of blood to an area brain.


The researchers team - led by Berislav Zlokovic,M.D., Ph.D., from the University of Southern California (USC) - releasing their findings in the journal Nature Medicine.

Stroke is the most common cause of death of people worldwide. According to the Centers for Disease Control and Prevention(CDC), stroke is the fifth leading cause of death in the United States and is also a major cause of disability in adults.

A human brain after having stroke. The brain cell damages on the right side and producing side effect to the left side.


The effects of a stroke depend on the location of the blockage and how much brain tissue is involved, but a stroke on one side of the brain will result in neurological effects on the opposite side of the body. For example, a stroke on the right side of the brain could produce paralysis on the left side of the body, and vice versa. Which is showing above in the image.

The process of the stem cell therapy lies on two methods

The researchers say their therapy is a combination of two methods. One involves surgically grafting human neural stem cells onto the damaged area, where they are able to mature into neurons another brain cells.

The other therapy uses a compound called3K3A-APC, which has been shown to help neural stem cells that have been grown in a petri dish grow into neurons. But the researchers say it was not clear what effect the molecule - called activated protein-C (APC) - would have on live animals.

A month after their strokes, mice that had received both the stem cells and 3K3A-APC performed significantly better on tests of motor and sensory functions compared to mice that received neither or only one of the treatments.. The researchers also observed that the mice given3K3A-APC had more stem cells survive and mature into neurons.

“This USC-led animal study could pave the way fora 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. “If the therapy works in humans, it could markedly accelerate the recovery of these patients.”

The researchers induced stroke-like brain damage in mice by disrupting blood flow to a specific part of their brains. One week later – the equivalent of several months in humans – the team inserted the stem cells next to the dead tissue and then gave the mice several infusions of either a placebo or 3K3A-APC.

"When you give these mice 3K3A-APC, it works much better than stem cells alone," says Dr. Zlokovic. "We showed that 3K3A-APC helps the cells convert into neurons and make structural and functional connections with the host's nervous system."

The results of stem cell therapy on mice brain are astonishing…!!

To confirm that the stem cells were responsible for the animals’ improved function, the researchers used a targeted toxin to kill the neurons that had developed from them in another group of mice given the combination therapy. These mice showed the same improved performance on the tests of sensory and motor functions prior to being given the toxin but lost these gains afterwards, suggesting that the neurons that grew from the implanted cells were necessary for the improvements.

The fusion of the compound 3K3A-APC and neural stem cells helped mice with stroke


In a separate experiment, the team examined the connections between the neurons that developed from the stem cells in the damaged brain region and nerve cells in a nearby region called the primary motor cortex. The mice given the stem cells and 3K3A-APC had many more neuronal connections, called synapses, linking these areas than mice given the placebo.

Then, when the researchers stimulated the mince's paws with a vibration, the neurons that grew from the stem cells exhibited a stronger response in the mice that were treated.

"That means the transplanted cells are being functionally integrated into the host's brain after treatment with 3K3A-APC. No one in the stroke field has ever shown this, so I believe this is going to be the gold standard for future studies." Dr. Berislav Zlokovic also added.

3K3A-APC is currently being studied in a NINDS-funded Phase II clinical trial to determine if it can reduce the death of neurons deprived of blood flow immediately following a stroke. As a result of the new mouse study, Dr. Zlokovic and his team, including co-first authors Yaoming Wang and Zhen Zhao, now hope to pursue another Phase II clinical trial to test whether the combination of neural stem cell grafts and 3K3A-APC can stimulate the growth of new neurons in human stroke patients to improve function. If that trial succeeds, it may be possible to test the treatment’s effects on other neurological conditions, such as spinal cord injuries, for which stem cell therapies are being investigated.

"This USC-led animal study could pave the way for a potential breakthrough in how we treat people who have experienced a stroke," says Jim Koenig, Ph.D., program director at the National Institute of Health's National Institute of Neurological Disorders and Stroke(NINDS), who funded the study.

"If the therapy works in humans," heads, "it could markedly accelerate the recovery of these patients."

The study was supported by the NIH (NS090904,NS075345, HL052246 and HL031950) with additional funding provided by the National Natural Science Foundation of China, the Adelson Medical Research Foundation, the New York State Stem Cell Research Board, the Novo Nordisk Foundation, the Lundbeck Foundation, the National Multiple Sclerosis Society,and the ALS Association.

Over view

There is no doubt that the therapeutic potential of stem cells has so profoundly changed the landscape of medical research. This process has spawned an entirely new field in the regenerative medicine.

Not only there is certainly a great deal of promise, but also a tendency to think that a cure is just around the corner.The way from research to the clinic is often long and complicated, with many small advances. Our aim is to present an objective view of the most important advances, to provide a foundation knowledge against which to read and evaluate new research as it emerges.


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