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Growing human brain cells in the lab to study neurodegenerative diseases

Researcher: Rawan Aloufi

Location: FRAME Lab, University of Nottingham

Microglial cells are brain cells involved in the development of neurodegenerative diseases, like Parkinson’s and Alzheimer’s disease. FRAME lab PhD student Rawan Aloufi has developed a technique to grow human microglia in the lab to study these diseases, which could replace many experiments involving animals.

The problem

Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and multiple sclerosis are all examples of neurodegenerative diseases. In these conditions, Inflammation in the brain can lead to the death of neurons, which leads to a decline in brain function and the development of dementia.

One cell type that researchers are interested in studying is microglia, which are immune cells found in the brain and spinal cord. Scientists believe that microglia may play an important role in the development of neurodegenerative diseases, but that it may also be possible to encourage microglia to protect people from such diseases.

Animal models, in particular those using mice and rats, have often been used to study microglia and neurodegenerative diseases.  But after multiple clinical trials of treatments for these diseases have failed, these animal models are being called into question. It is becoming clear they do not fully replicate human diseases.

On the other hand, human microglia are difficult to isolate from people to study in the lab. They can only be obtained from either invasive brain biopsies or from brain tissue after death, both of which are technically challenging, time-consuming, and do not produce enough cells to carry out significant research.

We need easier methods to obtain human microglia to study neurodegenerative diseases in the lab in ways that are more relevant to human disease.

“There are valid concerns about the applicability of animal disease models to human patients due to the failure of multiple treatment trials aimed at these neurodegenerative disorders.”

Dr Rawan Aloufi. 

The project

Dr Rawan Aloufi tested an alternative approach to obtaining microglia. She took human blood mononuclear cells, readily obtainable from the NHS blood transfusion service, and used a cocktail of chemicals and proteins to get them to transform into microglial cells.

In her PhD project, Rawan used these lab-grown microglia to study a particular group of proteins called Peroxisome Proliferator-Activated Receptors, or PPARs. Previous research has suggested that PPARs can reduce the inflammation in the brain that leads to the death of brain cells. What’s more, drugs that activate PPARs have potential as treatments for some neurodegenerative diseases. Rawan has been using her lab-grown microglia to study this further.

The potential

Rawan’s research project could reveal the potential of PPAR-activating drugs as treatments for neurodegenerative conditions. This could eventually help to slow down or stop the progression of these debilitating diseases.

Importantly, Rawan’s research has also tested an alternative approach to obtaining human microglia, by growing them from blood cells. This could lead to models for studying neurodegenerative diseases in the lab which better replicate these human conditions, without the use of animal models.

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