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Human stem cells for modelling neurological disease and its therapeutic applications

Speaker
  • Chief Technology Scientist, Centre for Brain development and Repair, Instem, Bangalore
    Biography
      Dr. Rakhi Pal is the Chief technology scientist at the Centre for Brain Development and Repair, Institute of Stem cell biology and Regenerative medicine, Bangalore,India where she works on using stem cell based technologies to develop platforms for understanding neuro-developmental disorders. A Gold medalist in Human Physiology from the prestigious All India Institute of Medical Sciences, New Delhi and a PhD from Manipal University, Dr Pal has more than 10 years of experience in the field of stem cell biology with particular interest in neurological disorders. She not only has multiple publications and patents to her name, but also possesses an unique blend of both industry and academic experiences.

    Abstract

    My talk shall encompass how the stem cell research field has evolved from embryonic stem cells to adult stem cells and currently induced pluripotent stem cells with special reference to the field of neuroscience in a bench to bedside approach. Studying neurological disorders has always been a challenge.  This is compounded by the lack of predictive pathophysiological models to identify and test potential therapeutic targets. Adult stem cells being multipotent and non-teratogenic have been in the limelight of stem cell clinical research. Multiple clinical trials have been conducted across the globe with limited inconsistent results. As we progress to understand how stem cells possibly orchestrate the regeneration process, it has opened up a whole new avenue of questions which I shall elaborate during the course of my talk. While, adult stem cells continue to be the focus of clinical trials at the moment, it is essential to mention that the discovery of induced pluripotent stem cells, has made the field even more exciting. Along with the technological advancements in sequencing and gene manipulation techniques, personalized medicine seems to be the future. Reconstruction of the early developmental stages is now possible by deriving induced human pluripotent stem cells from patient samples using advanced molecular and cellular manipulation methods. For eg: We, have been successful in reprogramming and differentiating human patient derived iPSC into the three common brain cell types- neurons, glial cells and oligodendrocytes of cortical origin, importantly using pathways and trophic factors that can sequentially recapitulate human neural development. This is imperative for accurate understanding of the disease and enhancement of therapeutic strategies.   Upon marker analysis and functional characterization, human iPSCs are able to consistently generate cortical neurons which are electrophysiologically active having intrinsic electrical properties comparable to adult human neurons and capable of generating mature action potentials upon stimulation. However, lack of synaptic activity lead us to further explore an astrocyte -neuronal co-culture system which closely mimics the internal milieu of the brain and responds to drugs. This platform is currently being used to understand pathophysiology of various neurological, neurodevelopmental and neurodegenerative disorders. Importantly, it opens up unlimited access to human tissue material in an unprecedented manner, which can be used for drug testing, neurotoxicity studies, epigenetic changes, gene editing studies and personalized medicine.


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