Research Group Successful in Using Cell Transplantation to Improve Therapeutic Efficacy in Chronic Spinal Cord Injury: Motor Function Recovered Through Combined Rehabilitation Treatment
February 14, 2023 Keio University School of Medicine
A research group at the Keio University School of Medicine has successfully transplanted human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) into mouse models of chronic spinal cord injury combined with rehabilitation using progressive-intensity treadmill training to restore motor function and reveal histological findings. The group was led by Professor Hideyuki Okano of the Department of Physiology, Professor Masaya Nakamura, Assistant Professor Narihito Nagoshi, research assistant Takahiro Shibata of the Department of Orthopaedic Surgery, and part-time lecturer Syoichi Tashiro of the Department of Rehabilitation Medicine.
The research group has previously reported on the efficacy of hiPSC-NS/PC transplantation for subacute spinal cord injury. However, the therapeutic effect of cell transplantation for chronic spinal cord injury with limited treatment sensitivity has been limited, and the need for combination therapy, such as drugs and rehabilitation, has been recognized. To optimize rehabilitation therapy, the group has developed a protocol of treadmill training with increasing intensity for a mouse model of spinal cord injury and has reported that this method improves motor function to some extent, with increased expression of neurotrophic factor and neural activity in the lumbar spinal cord, even in the chronic phase. The results of this study showed that the use of this method was effective in improving motor function to some extent, even in the chronic phase of spinal cord injury.
In this study, the group verified the efficacy of the combined treatment of rehabilitation and transplantation of hiPSC-NS/PCs of sufficient quality for clinical research using the aforementioned training method in a mouse model of chronic spinal cord injury. The combined use of rehabilitation therapy improved the survival rate of transplanted neural stem/progenitor cells and promoted their differentiation into mature neurons. In addition, more neurotrophic factors were expressed in the spinal cord tissues, including the injured area, and increased neuronal activity and serotonergic neuron fibers were observed in the spinal cord. As a result, the combined treatment of cell transplantation and rehabilitation showed better recovery of motor function than cell transplantation alone.
This study is the first report of a combined treatment of hiPSC-NS/PC transplantation and rehabilitation for chronic spinal cord injury, and the researchers believe it is a very significant achievement in establishing a therapeutic foundation for regenerative medicine for chronic spinal cord injury in the clinical setting.
The results of this research were published online in STEM CELLS Translational Medicine on January 17, 2023 (EST).
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