Experimental Stem Cell Therapy Repairs Brain Damage from Stroke and Dementia in Mice

Experimental Stem Cell Therapy Repairs Brain Damage from Stroke and Dementia in Mice

UCLA researchers have shown that a one-time stem cell therapy treatment can help to repair the brain damage caused by stroke and dementia in mice.

According to the World Health Organization, 50 million people worldwide have dementia and 10 million new cases are diagnosed each year. At any given time, around 5-8% of people over the age of 60 have dementia and it is the leading cause of death in the United Kingdom.

Dementia is an umbrella term for progressive conditions that damage nerve cells in the brain which prevents the brain from functioning normally. Dementia typically involves memory impairment and problems with attention, communication, and coordination and is usually fatal. Dementia can be caused by many different medical conditions, with the two leading causes being subcortical white matter stroke (WMS) and Alzheimer’s disease.

WMS accounts for around 30% of all stroke events and results in major damage to astrocytes, axons, and myelin, which typically leads to cognitive and motor impairment. There are currently no therapies available to stop the progression of WMS nor treatments that can repair the damage to the nerve cells in the brain after a WMS event has occurred.

UCLA researchers have shown in previous studies that immature astrocyte transplantation can promote remyelination in rodents. The researchers hypothesized that a therapeutic intervention targeting astrocytes could potentially help with brain repair in individuals after a WMS event.

Astrocytes are a type of glial cell that surround and support neurons and play a key role in many functions of the central nervous system. The researchers introduced these cells into mouse models of individuals in the early to middle stages of dementia to see if they helped limit brain damage and helped to activate repair processes.

The researchers found that repair processes were activated and the treatment, formation of new neural connections was enhanced, and myelin production was increased. Myelin is the fatty substance that surrounds and protects neural connections.

“Understanding the role that glia play in repairing white matter damage is a critically important area of research that needs to be explored,” said Francesca Bosetti, program director at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke. “These preliminary results suggest that glial cell-based therapies may one day help combat the white matter damage that many stroke and vascular dementia patients suffer every year.”

The researchers generated induced pluripotent stem cells (IPSCs) from skin and blood cells and differentiated the IPSCs into astrocytes using the drug deferoxamine. This technique could be used to generate large numbers of astrocytes quickly for use in treatments in humans as an off-the-shelf product. This is important, as treatment needs to be provided to patients quickly following a WMS event, as the damage caused is progressive and there is not time to develop patient-specific treatments.

This is possible because the immune response in the brain is tightly controlled in what is known as immune privilege. That means that while an immune response would be generated if donor cells were introduced in other parts of the body, they survive for longer in the brain and do not require patients to take drugs to suppress their immune system.

The researchers also found that if the injected astrocytes were eliminated from the brain months after treatment, the recovery of the treated mice was unaffected. This is because the injection of the astrocytes stimulated the brain’s repair processes and they were not directly involved in repairing the brain. The cells therefore do not need to persist for the treatment to be successful.

The researchers are now conducting further studies with a view to obtaining permission from the FDA for a clinical trial in humans.

You can read more about the study in the paper – Patient-derived glial enriched progenitors repair functional deficits due to white matter stroke and vascular dementia in rodents – which was recently published in the journal Science Translational Medicine. DOI: 10.1126/scitranslmed.aaz6747