Most studies targeting chronic spinal cord injury (SCI) have concluded that neural stem/progenitor cell (NS/PC) transplantation exerts only a subclinical recovery; this in contrast to its remarkable effect on acute and subacute SCI. To determine whether the addition of rehabilitative intervention enhances the effect of NS/PC transplantation for chronic SCI, we used thoracic SCI mouse models to compare manifestations secondary to both transplantation and treadmill training, and the two therapies combined, with a control group. Significant locomotor recovery in comparison with the control group was only achieved in the combined therapy group. Further investigation revealed that NS/PC transplantation improved spinal conductivity and central pattern generator activity, and that treadmill training promoted the appropriate inhibitory motor control. The combined therapy enhanced these independent effects of each single therapy, and facilitated neuronal differentiation of transplanted cells and maturation of central pattern generator activity synergistically. Our data suggest that rehabilitative treatment represents a therapeutic option for locomotor recovery after NS/PC transplantation, even in chronic SCI.
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http://dx.doi.org/10.1038/srep30898 | DOI Listing |
Inflamm Regen
March 2024
Department of Physiology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Inflamm Regen
October 2023
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Background: Human induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC)-based cell transplantation has emerged as a groundbreaking method for replacing damaged neural cells and stimulating functional recovery, but its efficacy is strongly influenced by the state of the injured spinal microenvironment. This study evaluates the impact of a dual therapeutic intervention utilizing hepatocyte growth factor (HGF) and hiPSC-NS/PC transplantation on motor function restoration following spinal cord injury (SCI).
Methods: Severe contusive SCI was induced in immunocompromised rats, followed by continuous administration of recombinant human HGF protein into the subarachnoid space immediately after SCI for two weeks.
Commun Biol
June 2023
Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan.
Although neural stem/progenitor cells derived from human induced pluripotent stem cells (hiPSC-NS/PCs) are expected to be a cell source for cell-based therapy, tumorigenesis of hiPSC-NS/PCs is a potential problem for clinical applications. Therefore, to understand the mechanisms of tumorigenicity in NS/PCs, we clarified the cell populations of NS/PCs. We established single cell-derived NS/PC clones (scNS/PCs) from hiPSC-NS/PCs that generated undesired grafts.
View Article and Find Full Text PDFN Am Spine Soc J
March 2023
Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
Spinal cord injury (SCI) has been considered to cause sudden, irreversible loss of function in patients. However, developments in stem cell biology and regenerative medicine are changing this conventional notion. Here we reviewed the overview of regenerative medicine of SCI.
View Article and Find Full Text PDFNeurosurg Rev
December 2022
Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Poursina Ave., Tehran, Iran.
Background: This present study evaluates the pre-clinical evidence on the efficacy of NS/PC and scaffold (NS/PC + scaffold) transplantation on locomotor recovery after traumatic spinal cord injury (SCI).
Method: Two independent reviewers screened the records gathered through a systematic search in MEDLINE, Embase, Scopus, and Web of Sciences databases. Studies on rats/mice evaluating the efficacy of simultaneous transplantation of NS/PCs and scaffold in the treatment of SCI were included.
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