Neuronal degeneration and the deterioration of neuronal communication lie at the origin of many neuronal disorders, and\nthere have been major efforts to develop cell replacement therapies for treating such diseases. One challenge, however, is\nthat differentiated cells are challenging to transplant due to their sensitivity both to being uprooted from their cell culture\ngrowth support and to shear forces inherent in the implantation process. Here, we describe an approach to address these\nproblems. We demonstrate that rat hippocampal neurons can be grown on colloidal particles or beads, matured and even\ntransfected in vitro, and subsequently transplanted while adhered to the beads into the young adult rat hippocampus. The\ntransplanted cells have a 76% cell survival rate one week post-surgery. At this time, most transplanted neurons have left\ntheir beads and elaborated long processes, similar to the host neurons. Additionally, the transplanted cells distribute\nuniformly across the host hippocampus. Expression of a fluorescent protein and the light-gated glutamate receptor in the\ntransplanted neurons enabled them to be driven to fire by remote optical control. At 1-2 weeks after transplantation,\ncalcium imaging of host brain slice shows that optical excitation of the transplanted neurons elicits activity in nearby host\nneurons, indicating the formation of functional transplant-host synaptic connections. After 6 months, the transplanted cell\nsurvival and overall cell distribution remained unchanged, suggesting that cells are functionally integrated. This approach,\nwhich could be extended to other cell classes such as neural stem cells and other regions of the brain, offers promising\nprospects for neuronal circuit repair via transplantation of in vitro differentiated, genetically engineered neurons.
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