Functional Neuron Replacement to Rejuvenate the Neocortex

Photo by Erin Ashford

Albert Einstein College of Medicine

Principal Investigator: Dr. Jean Hébert
Research TeamHiroko Nobuta, Joanna Krzyspiak, Alexander Quesada, Marta Gronska-Peski, Jayleecia Smith

Of all the challenges in cell therapy, replacement of neurons in the neocortex is both the most important (the brain being the seat of consciousness and identity) and perhaps the most formidable. Only recently have any researchers succeeded in integrating new neurons into this area of the brain. Moreover, the vast majority of transplanted cells in these cases have failed to survive, and the few survivors have achieved only limited function and integration into existing circuits.

SRF is now supporting Dr. Jean Hébert’s work to advance two innovative strategies to address different aspects of the challenge. First, Dr. Hébert’s team will transplant neuronal precursors (from both mice and humans) along with precursors of the blood vessels needed to nourish new neurons, in order to enhance their survival and integration. Second, because new neurons will be needed throughout the aging neocortex but transplanting neurons throughout the entire tisssue would be extremely invasive and risk injury to a tissue we cannot afford to damage, the AECOM team will engineer microglia (which, unlike neurons and their precursors, are highly mobile cells) to disperse widely from the site of transplant and then be reprogrammed into cortical projection neurons at their destination. From there, the team will characterize the integration of the transplanted microglia-cum-neurons into host circuits of converted neurons derived from our engineered transplanted microglia, and determine whether depleting host microglia enhances these processes in different models.

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