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How disease-in-a-dish model could help treat brain disorders
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How disease-in-a-dish model could help treat brain disorders

The discovery of induced pluripotent stem cells has made it possible for scientists to study and understand different brain disorders at a cellular and molecular level.
stem cells in neurobiology
Representational Image | Shutterstock

In 2006, Japanese researcher and physician Shinya Yamanaka developed a technique to convert any cell in the body into a potential stem cell, opening the floodgates for stem cell research.  

Stem cells are unique: they originate in the early embryonic stage and possess the ability to develop into any type of body cell, such as liver, brain or muscle cells. Initially, these ‘pluripotent cells’ were sought after for research studies, but controversies around the use of embryos to source them made researchers look for alternative techniques. Yamanaka’s new technique overcame these hurdles allowing research to pick up pace. 

Yamanaka employed a reverse engineering technique to give a new avatar to mature body cells. In their initial experiments, he and his student Kazutoshi Takahashi introduced four critical genes into mouse skin cells. They then reprogrammed the genes in the cells and, in a process called transduction, turned them into potential stem cells called induced pluripotent stem cells (iPSCs).   

A year later (2007) they succeeded in obtaining iPSCs from human skin cells. Thanks to Yamanaka’s significant discovery, scientists can now take any cell in the body and get the starting material to study human diseases or test new drugs in a lab dish.  

To do this, scientists use easily accessible cells like skin and blood cells as the starting point. “We can make iPSCs starting from any somatic (body) tissue,” Dr Raghu Padinjat, Professor and Dean of Research at National Centre for Biological Sciences (NCBS), Bangalore, tells Happiest Health. “We collect a blood sample, isolate white blood cells in the laboratory, and then reprogramme those white blood cells to give iPSCs,” he explains.  

iPSCs in the study of brain disorders 

Before the discovery of iPSCs, scientists had to use mice to study human brain disorders. However, the human brain is a complex organ and mice models are not a good fit to study these complexities. On the other hand, obtaining human brain cells was difficult as it required invasive techniques like biopsies. 

At such time, iPSCs became a valuable tool to study disease mechanisms in the brain. iPSCs give cellular and molecular level insights and enable identifying gene mutations responsible for different diseases. Neurodegenerative diseases such as Parkinson’s and Alzheimer’s are being widely studied using iPSC-derived neurons to better understand the effect of specific gene mutations on the disease. 

“For instance, if you are interested in studying dopamine release in Parkinson’s disease, iPSCs can provide the starting material to generate the neurons affected in the disease,” says Dr Padinjat.  

From a clinical aspect, early detection is the key to diagnosing neurodegenerative disorders. Most of these diseases have late physical manifestations — after several changes in the cells and tissue have already occurred.  “Even the most high-resolution MRI machines can only detect the changes that occur in tissue and specific brain regions affected in these diseases,” Dr Padinjat says. 

Using iPSC-derived neurons from affected individuals helps in understanding key disease mechanisms in these disorders, he adds.  

iPSCs as drug testing platforms 

iPSC could hold the key to finding personalised treatments for individuals affected by these conditions. Currently, our limited understanding of these conditions makes it difficult to develop more targeted drug treatments.  

Researchers are trying to capture the insights of the genetic information of neuropsychiatric conditions of the affected individual by using a ‘disease-in-a-dish’ model with iPSCs. Changes that occur in the gene can be linked to the physiological changes in the person. 

“By testing out drugs on an iPSC model, we get a better idea of what drugs may work by taking the persons genetics into account,” says Dr Padinjat.  

Dr Nishant Singhal, scientist and group leader at the National Centre for Cell Science, Pune whose lab works on iPSCs concurs. “We can use iPSCs to test drugs on human cells and understand its efficacy and toxicity,” he says. Such a lab model can help researchers develop targeted drugs faster. 

The road ahead 

As with any developing technology, iPSCs, too, have limitations. We are still far from using iPSC derived cells to directly replace cells lost in neurodegenerative disorders.  

Dr Singhal whose primary focus is on developing treatments for neurological disorders using iPSC’s, says “We need to work on generating the right types of nerve cells. If you want to inject them into the brain it still needs to migrate to the specific brain regions that are degenerating.” 

Even with some of these limitations, scientists are working to better understand what the underlying causes of different neurological illnesses are. The potential of iPSC in brain disorder research has opened new avenues to explore. 

For now, iPSC technology is proving to be successful in studying diseases in the lab. By uncovering disease mechanisms and identifying new drug targets, the use of this cell system brings us closer to understanding and treating complex brain disorders.  

“Once you have derived iPSCs from an individual that has mutation in a gene, it becomes easier to study their disease pathology in a dish and you can have a much better chance of developing a treatment for those individuals. Since human iPSCs technology can be applied to understand any disease, it provides unlimited potential for developing treatments,” says Dr Singhal. 

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