TY - JOUR
T1 - A non-invasive system to monitor in vivo neural graft activity after spinal cord injury
AU - Ago, Kentaro
AU - Nagoshi, Narihito
AU - Imaizumi, Kent
AU - Kitagawa, Takahiro
AU - Kawai, Momotaro
AU - Kajikawa, Keita
AU - Shibata, Reo
AU - Kamata, Yasuhiro
AU - Kojima, Kota
AU - Shinozaki, Munehisa
AU - Kondo, Takahiro
AU - Iwano, Satoshi
AU - Miyawaki, Atsushi
AU - Ohtsuka, Masanari
AU - Bito, Haruhiko
AU - Kobayashi, Kenta
AU - Shibata, Shinsuke
AU - Shindo, Tomoko
AU - Kohyama, Jun
AU - Matsumoto, Morio
AU - Nakamura, Masaya
AU - Okano, Hideyuki
N1 - Funding Information:
The authors thank S. Yamanaka at CiRA (Kyoto University) for supplying the 414C2 human iPSCs. We thank K. Tanaka at the Department of Psychiatry (Keio University) for technical and conceptual guidance. We thank H. J. Okano and M. Hasegawa at the Division of Regenerative Medicine (Jikei University) for their assistance with the experiments. We thank Y. Sato and K. Nagashima at the Department of Preventive Medicine and Public Health (Keio University) for statistical advice. We are grateful for the assistance of H. Miyoshi, S. Nori, O. Tsuji, S. Ito, Y. Hoshino, Y. Tanimoto, T. Shibata, S. Hashimoto, Y. Suematsu, Y. Saijyo, T. Nishijima, T. Tanaka, K. Ito, L. Tao, and K. Nakanishi, who are all members of the spinal cord research team at the Department of Orthopaedic Surgery and Physiology (Keio University). We also thank T. Harada, K. Yasutake, and M. Akizawa for their assistance with the experiments and animal care. This work was supported by the Japan Agency for Medical Research and Development (AMED) (grant nos. JP20bm0204001, JP19bm0204001, JP20bk0104017, and JP19bk0104017 to H.O. and M.N.; grant no. JP20bm0704046 to S.S. and T.S.; grant no. JP18dm0207036 to H.B.), the Japan Society for the Promotion of Science (JSPS) (KAKENHI grant number 22H03205 to N.N.; 17H06312 to H.B.), and the General Insurance Association of Japan (Medical Research Grant 2018 to K.A.)
Funding Information:
The authors thank S. Yamanaka at CiRA (Kyoto University) for supplying the 414C2 human iPSCs. We thank K. Tanaka at the Department of Psychiatry (Keio University) for technical and conceptual guidance. We thank H. J. Okano and M. Hasegawa at the Division of Regenerative Medicine (Jikei University) for their assistance with the experiments. We thank Y. Sato and K. Nagashima at the Department of Preventive Medicine and Public Health (Keio University) for statistical advice. We are grateful for the assistance of H. Miyoshi, S. Nori, O. Tsuji, S. Ito, Y. Hoshino, Y. Tanimoto, T. Shibata, S. Hashimoto, Y. Suematsu, Y. Saijyo, T. Nishijima, T. Tanaka, K. Ito, L. Tao, and K. Nakanishi, who are all members of the spinal cord research team at the Department of Orthopaedic Surgery and Physiology (Keio University). We also thank T. Harada, K. Yasutake, and M. Akizawa for their assistance with the experiments and animal care. This work was supported by the Japan Agency for Medical Research and Development (AMED) (grant nos. JP20bm0204001, JP19bm0204001, JP20bk0104017, and JP19bk0104017 to H.O. and M.N.; grant no. JP20bm0704046 to S.S. and T.S.; grant no. JP18dm0207036 to H.B.), the Japan Society for the Promotion of Science (JSPS) (KAKENHI grant number 22H03205 to N.N.; 17H06312 to H.B.), and the General Insurance Association of Japan (Medical Research Grant 2018 to K.A.)
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85135769469&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-03736-8
DO - 10.1038/s42003-022-03736-8
M3 - Article
C2 - 35948599
AN - SCOPUS:85135769469
SN - 2399-3642
VL - 5
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 803
ER -