Novel System to Monitor In Vivo Neural Graft Activity After Spinal Cord Injury

Ago, K.; Nagoshi, N.; Imaizumi, K.; Kitagawa, T.; Kawai, M.; Kajikawa, K.; Shibata, R.; Kamata, Y.; Kojima, K.; Shinozaki, M.; Kondo, T.; Iwano, S.; Miyawaki, A.; Ohtsuka, M.; Bito, H.; Kobayashi, K.; Shibata, S.; Shindo, T.; Kohyama, J.; Matsumoto, M.; Nakamura, M.; Okano, H.

doi:10.1101/2021.08.29.458127

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bioRxiv · 10.1101/2021.08.29.458127

Novel System to Monitor In Vivo Neural Graft Activity After Spinal Cord Injury

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Abstract

Expectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host, and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under control of a potent neuronal activity-dependent synthetic promoter, E-SARE, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we reveal that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI and determine better therapy techniques that maximize the function of cells in the host circuit.

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Ago, K., Nagoshi, N., Imaizumi, K., Kitagawa, T., Kawai, M., Kajikawa, K., Shibata, R., Kamata, Y., Kojima, K., Shinozaki, M., Kondo, T., Iwano, S., Miyawaki, A., Ohtsuka, M., Bito, H., Kobayashi, K., Shibata, S., Shindo, T., Kohyama, J., Matsumoto, M., Nakamura, M., Okano, H.. 2021-08-31. Novel System to Monitor In Vivo Neural Graft Activity After Spinal Cord Injury. https://doi.org/10.1101/2021.08.29.458127

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