February 3, 2023
Keio University School of Medicine
A research group led by Professor Hideyuki Okano of the Department of Physiology, Professor Masaya Nakamura, Senior Lecturer Narihito Nagoshi, and Assistant Professor Takahiro Shibata of the Department of Orthopedic Surgery, and Part-time Lecturer Shoichi Tashiro of the Department of Rehabilitation Medicine, all from the Keio University School of Medicine, has successfully restored motor function and histological findings in chronic spinal cord injury model mice by transplanting human iPS cell-derived neural stem/progenitor cells and combining this with rehabilitation involving progressively intensive treadmill gait training.
Previously, this research group had reported the efficacy of transplanting human iPS cell-derived neural stem/progenitor cells for subacute spinal cord injury. However, the therapeutic effect of cell transplantation for chronic spinal cord injury, which has poor therapeutic sensitivity, was limited, and the need for combination therapies such as drugs and rehabilitation had been pointed out. To optimize rehabilitation therapy, the research group had previously developed a method of progressively intensive treadmill gait training for spinal cord injury model mice. They had reported that using this method, even in the chronic phase, exerted a certain degree of motor function improvement, accompanied by increased neurotrophic factor expression and neural activity in the lumbar spinal cord. In this study, the group performed a combination therapy of transplanting human iPS cell-derived neural stem/progenitor cells of a quality level suitable for clinical research and rehabilitation using the aforementioned training method in chronic spinal cord injury model mice, and verified its effects. The combination with rehabilitation therapy improved the survival rate of the transplanted neural stem/progenitor cells and promoted their differentiation into mature neurons. Furthermore, more neurotrophic factors were expressed within the spinal cord tissue, including the injured area, and enhanced neural activity within the spinal cord and an increase in raphespinal tract nerve fibers were observed. As a result, the combination therapy of cell transplantation and rehabilitation showed superior motor function recovery compared to cell transplantation alone.
This study is the first report to investigate the combination therapy of human iPS cell-derived neural stem/progenitor cell transplantation and rehabilitation for chronic spinal cord injury. We believe this is a very significant achievement in establishing a therapeutic foundation for regenerative medicine for chronic spinal cord injury in clinical practice.
The results of this research were published in the online edition of STEM CELLS Translational Medicine on January 17, 2023 (US Eastern Time).
For the full press release, please see below.