Stimulation of Transplanted Human iPSC-derived Neural Cells Successfully Improves Therapeutic Effects in Spinal Cord Injury: Enhancing Synaptic Activity through Selective Stimulation of Transplanted Cells Using Synthetic Receptor Technology
December 24, 2021
Keio University School of Medicine
A research team at Keio University School of Medicine has succeeded in transplanting human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSCNS/PCs) into mice with spinal cord injury (SCI) to promote motor function recovery by stimulating the transplanted cells from outside the body using a synthetic receptor technology called DREADDs to repeatedly increase the activity of the transplanted cells. The team was led by Professor Masaya Nakamura of the Department of Orthopedic Surgery, Professor Hideyuki Okano of the Department of Physiology, Instructor Momotaro Kawai, and Assistant Professor Narihito Nagoshi.
The research team has previously reported on the efficacy of transplanting hiPSCNS/PCs into animal models of subacute SCI to improve motor function. Here, the team conducted a detailed study that focused on the activity of hiPSC-NS/PCs following transplantation. They then introduced the DREADD gene and consecutively and selectively stimulated transplanted hM3Dq-NS/PCs in mouse models following subacute SCI. The results showed increased synaptic activity and improved locomotor function in the stimulated animals when compared with the group of mice that had only undergone conventional transplantation.
The results of this study reveal the importance of hiPSC-NS/PCs activity and of synaptic activity between transplanted cells and the surrounding host tissue for SCI. These findings provide a strategy for developing therapies aimed at improving the efficacy of cell transplantation therapy for SCI. The results of this research were published online on November 23, 2021 (EST), in the open-access journal Cell Reports.
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