Repeated Transplantation of Human Cranial Bone-Derived Mesenchymal Stem Cells Improved Motor Function and Electrophysiological Recovery in Spinal Cord Injury Rat Model

Abstract

Background Mesenchymal stem cell (MSC)-based therapy has been applied in several clinical trials of spinal cord injury (SCI). We successfully established MSCs from human cranial bone and developed a longitudinal neuromonitoring technique for rodents. Recent studies have suggested the possibility of multiple transplantations as a new therapeutic strategy in addition to single transplantation. However, to our knowledge, there are no reports on the electrophysiological effects of multiple MSCs transplantation in SCI using transcranial electrical stimulation motor-evoked potentials (tcMEPs). Therefore, this study aimed to elucidate the efficacy and mechanism of action of multiple transplantation using this novel technique. Methods SCI rat model was established using the weight-drop method, and human cranial bone-derived MSCs (hcMSCs) were repeatedly transplanted intravenously on days 1 and 3 after SCI. Motor function and electrophysiological recovery of tcMEP were evaluated at 42 weeks post-transplantation. Tissue repair after SCI was assessed using immunostaining for myelin and neurons in the injured posterior cord. Results Repeated transplantation of hcMSCs significantly improved motor function and electrophysiological recovery than in single transplantation and control groups. In addition, this study reveals that repeated hcMSCs transplantation promotes electrophysiological functional recovery by exerting a protective effect on the functional structure of axons involved in the pyramidal tract. Conclusions Acute-phase repeated transplantation is expected to be a novel and effective therapeutic strategy for the clinical application of MSCs in SCI.