A non-invasive system to monitor in vivo neural graft activity after spinal cord injury

Kentaro Ago, Narihito Nagoshi, Kent Imaizumi, Takahiro Kitagawa, Momotaro Kawai, Keita Kajikawa, Reo Shibata, Yasuhiro Kamata, Kota Kojima, Munehisa Shinozaki, Takahiro Kondo, Satoshi Iwano, Atsushi Miyawaki, Masanari Ohtsuka, Haruhiko Bito, Kenta Kobayashi, Shinsuke Shibata, Tomoko Shindo, Jun Kohyama, Morio MatsumotoMasaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticlepeer-review

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 the control of enhanced synaptic activity-responsive element (E-SARE), a potent neuronal activity-dependent synthetic promoter, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we found 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.

Original languageEnglish
Article number803
JournalCommunications biology
Volume5
Issue number1
DOIs
Publication statusPublished - 2022 Dec

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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