Abstract
Stem cell therapy has been shown to reverse the sequelae of spinal cord injury (SCI). Although the ideal treatment route remains unknown, providing a large number of stem cells to the injured site using less invasive techniques is critical to achieving maximal recovery. This study was conducted to determine whether administration of bone marrow stem cell (BMSC) sheet made on its own without a scaffold is superior to intramedullary cell transplantation in a rat subacute SCI model. Adult female Sprague-Dawley rats were subjected to SCI by 30 g clip compression at the level of Th6 and Th7 and were administered BMSC cell sheet (7 × 104 cells, subdural), cell suspension (7 × 104 cells, intramedullary), or control seven days after the injury. Motor and sensory assessments, as well as histological evaluation, were performed to determine the efficacy of the different cell transplantation procedures. While both the cell sheet and cell intramedullary injection groups showed significant motor recovery compared to the control group, the cell sheet group showed better results. Furthermore, the cell sheet group displayed a significant sensory recovery compared to the other groups. A histological evaluation revealed that the cell sheet group showed smaller injury lesion volume, less inflammation, and gliosis compared to other groups. Sensory-related fibers of μ-opioid receptors (MOR, interneuron) and hydroxytryptamine transporters (HTT, descending pain inhibitory pathway), located around the dorsal horn of the spinal cord at the caudal side of the SCI, were preserved only in the cell sheet group. Stem cells could also be found inside the peri-injured spinal cord in the cell sheet group. BMSC cell sheets were able to promote functional recovery and palliate neuropathic pain more effectively than intramedullary injections, thus serving as a good treatment option for SCI.
Highlights
More than one million patients in the world suffer from paralysis caused by spinal cord injury (SCI) [1]
The cell sheet group showed significant motor functional recovery compared to the intramedullary injection and control groups starting from one week after transplantation, whereas the intramedullary injection group did not show a significant recovery compared to the control group until 6 weeks after transplantation (Figure 2(a))
Compared to the control group, the cell sheet group showed a significant reduction in injury lesion length (Figures 3(a)–3(d)) and lesion volume (Figure 3(e)) determined by the discontinuation of Luxol fast blue staining (LFB) staining 7 weeks from the insult (p < 0:01)
Summary
More than one million patients in the world suffer from paralysis caused by spinal cord injury (SCI) [1]. The cell transplantation methods, such as the type of cells, doses, transplantation routes, and timing, vary between trials and there is no consolidated consensus on the safest and most effective treatment strategy, intramedullary injection remains the most popular route of transplantation. This is because intramedullary transplantation has shown superiority in delivering the highest number of cells and providing greater functional recovery over intravascular
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