November 30, 2018
Keio University School of Medicine
Japan Agency for Medical Research and Development
A research group led by Professor Hideyuki Okano of the Department of Physiology and Professor Masaya Nakamura of the Department of Orthopedic Surgery at the Keio University School of Medicine has successfully restored and maintained motor function in a chronic spinal cord injury mouse model, which previously showed no therapeutic effect from cell transplantation alone. This was achieved solely by transplanting neural stem/progenitor cells derived from human iPS cells that were pre-treated with a Notch signaling inhibitor.
Previously, while the research group had confirmed the effectiveness of transplanting human iPS cell-derived neural stem/progenitor cells alone for spinal cord injury in the subacute phase (within a few weeks of injury), its efficacy in the chronic phase could not be confirmed. To date, there have been very few reports worldwide of functional improvement with cell transplantation therapy alone. It has been believed that cell transplantation alone is ineffective for chronic spinal cord injury, and that if the subacute phase is missed, neural stem cell transplantation is not feasible or would be ineffective even if performed.
In this study, the research group focused on the fact that pre-treating neural stem/progenitor cells to inhibit Notch signaling, one of the intercellular communication pathways, not only significantly promotes their differentiation into neurons but also facilitates axonal regeneration. They then transplanted human iPS cell-derived neural stem/progenitor cells, pre-treated with a Notch signaling inhibitor, into the chronically injured spinal cord. They discovered that even in the harsh environment where regeneration and motor function recovery are considered difficult, this led to axonal regeneration and elongation, and also induced remyelination.
The results of this research reveal the potential for patients with chronic spinal cord injury, long after the initial injury, to recover and maintain motor function. This is an unprecedented and significant achievement toward the clinical application of human iPS cell-derived neural stem/progenitor cell transplantation.
This research was published in the online edition of "Stem Cell Reports," the official journal of the International Society for Stem Cell Research (ISSCR), on November 29, 2018 (US Eastern Time).
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