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Laura Grabel


Neuroscience & Behavior


Temporal lobe epilepsy is characterized by recurrent seizures associated with loss of or damage to inhibitory interneurons in the hippocampus. Many researchers have proposed using neural progenitors derived from embryonic stem cells (ESCs) for cell replacement therapy in a number of neurodegenerative diseases, including temporal lobe epilepsy. Prior research in our laboratory has shown that a co-culture system of mouse cortical astrocytes and human embryonic stem cell (hESC)-derived neural progenitors (hESNPs) can assist in the maturation and differentiation of these hESC-derived inhibitory interneuron progenitors (Chen et al., 2016; Moakley, 2015). Although we are able to generate inhibitory interneurons and interneuron subtypes such as calbindin-expressing and somatostatin-expressing cells, we typically get a low yield of interneuron subtypes and a range in maturity within the culture. Research has shown that neuronal survival and differentiation are highly dependent on synaptic integration of the progenitors (Cellerino et al., 1992; Marty et al., 1997; Wamsley and Fishell, 2017; Zheng, 2014). We hypothesized that a triple culture in vitro model system, including mouse hippocampal cells, in addition to mouse cortical astrocytes, would provide a more heterogeneous environment, including a synaptic target, mimicking the host brain more closely, and therefore promote further generation of inhibitory interneurons from hESNPs. We found, however, that the addition of hippocampal cells promotes neural stem cell maintenance and proliferation, without maturation.



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