Personalized Neuroscience: Are Human-Derived Brain Organoids The Answer?
Brain organoids are pin-sized three dimensional self-organizing structures composed of roughly 2.5 million neural cells. They are derived from and genetically distinct to an individual. And while many open questions remain, they could represent a unique model for personalized neuroscience.
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Imagine a futuristic society capable of curing devastating neurological disorders by recreating the brains’ of patients in a dish. Doing so allows them to tailor drug cocktails and therapeutic strategies to the specifics of each individual. Personalized neuroscience providing customized treatments. Except it is not a futuristic society. It sounds like it should be, but in fact it is real science taking place right now across a number of labs throughout the world.
Brain organoids are pin-sized three dimensional self-organizing structures composed of roughly 2.5 million neural cells. They were originally created from human embryonic pluripotent stem cells, cells that are capable of forming every cell in the body. More recent methods are able to generate brain organoids from induced pluripotent stem cells reprogrammed from somatic donor cell types. This means that beginning with terminally differentiated cells, such as skin cells, genetic and cellular reprogramming can be achieved by carefully orchestrated exposure to specific sets of transcription factors and chemical environments. This results in the de-differentiation of the initial (for example, skin) cells back to an embryonic-like pluriopotent stem cell state.
Then the process is reversed: the induced stem cells are subsequently guided to differentiate into different types of neurons and other neural cells. The developmental genetic program - or at least certain aspects of it - is recapitulated in a dish and results in three dimensional structures that spontaneously self-organize at a cellular scale into anatomical structures that resemble aspects of the prenatal brain. For example, there is a distinctly defined cortical plate on the surface of the organoids, with a central cavitation resembling a ventricle, the fluid filled spaces in the brain that produce and recirculate cerebral spinal fluid. Beyond the brain, other efforts are developing organoid models in a similar way for different tissues and organs, such as the heart.
