Neurology Central

Cellular reprogramming to model the human brain in vitro: an interview with Cedric Bardy

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In this interview, Cedric Bardy, the Director of the Laboratory for Human Neurophysiology and Genetics at SAHMRI Mind & Brain in Australia, discusses progresses in stem cell reprogramming technologies that have the potential to lead to the discovery of new clinical treatments for neurological and psychiatric disorders.

Could you tell us a little about your career to date and what drew you into the field of neuroscience?

The complexity and power of the human brain fascinates me. I spent many years as a junior researcher scrutinizing how neural circuits process sensory inputs to create coherent visual perception, olfaction, movement and memories. It’s incredible that even the most powerful computers do not compete with the ordinary tasks that the human brain can perform. The brain is also beautifully designed to adapt to a wide range of changing biological conditions.

However, in some instances such brain plasticity reaches its limits and fails to maintain a balanced healthy neuronal activity. The consequences are serious and manifest in a variety of debilitating neurological disorders such as Parkinson’s disease, Alzheimer’s disease or depression. My lab is investigating the possibilities that some individuals have specific genetic predispositions that make it harder to cope with biological stressors and maintain a balanced brain activity. Understanding these molecular mechanisms at the cellular level will provide solid basis to discover medical alternative that will help patients coping with serious brain disorders.

Why is stem cell research important for your work?

To increase our chances of discovering new efficient medical treatments, we must diversify experimental models. Human cell reprogramming technologies have rapidly become a vital element in the medical researchers’ toolkit, especially in the field of neuroscience, where access to human brain biopsies is limited. The potential to unlimited access of live human neuronal tissue in vitro with stem cell technologies give new hopes for better understanding of neurological disorders.

“Human cell reprogramming technologies have rapidly become a vital element in the medical researchers’ toolkit, especially in the field of neuroscience, where access to human brain biopsies is limited.”

What does your current role entail?

I have been fortunate to join the pioneering lab of Professor Fred Gage at the Salk Institute (CA, USA) at an exciting time, when iPSC technology breakthrough unlocked new, wide research possibilities. I also quickly realized that despite the hype and hope in the neural stem cell field, the current in vitro models were quite distant from basic neurophysiological conditions in vivo.

To really take advantage of the full capability of powerful neural in vitro models, tissue culture conditions need to be optimized. Reducing the artificial gap between in vitro and in vivo models is essential because more physiological models relevant to human diseases will increase our chances of translational success. There is a pressing societal need to discover new treatments for neurological and psychiatric disorders: my lab aims to improve research biotechnologies and directly apply them to tackle brain disorders such as Parkinson’s disease and major depression. Our main objective is to better understand the complex biology of the human neurons in the context of mental health and neurological disorders.

“Reducing the artificial gap between in vitro and in vivo models is essential because more physiological models relevant to human diseases will increase our chances of translational success.”

Do you think that reprogramming with non-DNA methodologies is the future, owing to the reduced risk of genetic mutations and abnormal expression compared with methods using viruses and vectors?

Cellular reprogramming and expansion in vitro may introduce undesired genetic mutations. Such artificial mutations may bias analysis in disease models or add hazards for cell transplantation therapies. This risk may be significantly reduced by using a non-integrating viral vector (e.g., Sendai virus) or non-DNA methodologies to reprogram cells into iPSCs. In addition, particular care should also be drawn towards mutations that might occur spontaneously, in particular during cell divisions [1].

View the full interview on RegMetNet

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