Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov 23;37(8):110019.
doi: 10.1016/j.celrep.2021.110019.

Long-term selective stimulation of transplanted neural stem/progenitor cells for spinal cord injury improves locomotor function

Momotaro Kawai  1 , Kent Imaizumi  2 , Mitsuru Ishikawa  2 , Shinsuke Shibata  3 , Munehisa Shinozaki  2 , Takahiro Shibata  1 , Shogo Hashimoto  1 , Takahiro Kitagawa  1 , Kentaro Ago  1 , Keita Kajikawa  1 , Reo Shibata  1 , Yasuhiro Kamata  1 , Junichi Ushiba  4 , Keisuke Koga  5 , Hidemasa Furue  5 , Morio Matsumoto  6 , Masaya Nakamura  6 , Narihito Nagoshi  7 , Hideyuki Okano  8
Affiliations
Free article

Long-term selective stimulation of transplanted neural stem/progenitor cells for spinal cord injury improves locomotor function

Momotaro Kawai et al. Cell Rep. .
Free article

Abstract

In cell transplantation therapy for spinal cord injury (SCI), grafted human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) mainly differentiate into neurons, forming synapses in a process similar to neurodevelopment. In the developing nervous system, the activity of immature neurons has an important role in constructing and maintaining new synapses. Thus, we investigate how enhancing the activity of transplanted hiPSC-NS/PCs affects both the transplanted cells themselves and the host tissue. We find that chemogenetic stimulation of hiPSC-derived neural cells enhances cell activity and neuron-to-neuron interactions in vitro. In a rodent model of SCI, consecutive and selective chemogenetic stimulation of transplanted hiPSC-NS/PCs also enhances the expression of synapse-related genes and proteins in surrounding host tissues and prevents atrophy of the injured spinal cord, thereby improving locomotor function. These findings provide a strategy for enhancing activity within the graft to improve the efficacy of cell transplantation therapy for SCI.

Keywords: DREADD; cell transplantation therapy; chemogenetics; functional recovery; hM3Dq; human iPS cell; neural stem/progenitor cell; selective stimulation; spinal cord injury; synaptic transmission.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests J.U. is one of the founders and the Representative Director of Connect Inc., received a salary from, and holds shares of Connect Inc. M.N. declares a consultancy role with K-Pharma Inc. and research funding from RMic and Hisamitsu. H.O. declares a leadership position at Keio University School of Medicine and is a compensated scientific consultant for San Bio Co. Ltd. and K Pharma Inc. These companies have no relationship with the present study. The other authors declare no competing interest.

Publication types

MeSH terms