Abstract
BackgroundMesenchymal stem cells are widely used for transplantation into the injured spinal cord in vivo model and for safety, many human clinical trials are continuing to promote improvements of motor and sensory functions after spinal cord injury. Yet the exact mechanism for these improvements remains undefined. Neurogenic bladder following spinal cord injury is the main problem decreasing the quality of life for patients with spinal cord injury, but there are no clear data using stem cell transplantation for the improvement of neurogenic bladder for in vivo studies and the clinical setting.The purpose of this study was to delineate the effect of human mesenchymal stem cell (hMSCs) transplantation on the restoration of neurogenic bladder and impaired hindlimb function after spinal cord contusion of rats and the relationship between neurotrophic factors such as brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and bladder and hindlimb functions.ResultsModified moderate contusion injury were performed on the thoracic spinal cord of Sprague-Dawley rats using MASCIS impactor and hMSCs, human fibroblasts or phosphate-buffered saline were transplanted into injured spinal cord 9 days after injury for hMSC and two control groups respectively. Ladder test showed more rapid restoration of hindlimb function in hMSC group than in control group, but Basso, Beattie, and Bresnahan score and coupling score were not different significantly among hMSC and two control groups. Neurogenic bladder was not improved in either group. ED1 positive macrophages were significantly reduced in hMSC group than in two control groups, but ELISA and RT-PCR studies revealed BDNF and NT-3 levels in spinal cord and bladder were not different among hMSC and two control groups regardless the experimental duration.ConclusionhMSC transplantation was effective in reducing inflammatory reaction after spinal cord contusion of rats but not sufficient to recover locomotor and bladder dysfunction. BDNF and NT-3 levels in the spinal cord and bladder were not increased 28 and 56 days after hMSC transplantation.
Highlights
Mesenchymal stem cells are widely used for transplantation into the injured spinal cord in vivo model and for safety, many human clinical trials are continuing to promote improvements of motor and sensory functions after spinal cord injury
Bladder volume and urodynamic study Urodynamic study at PTD26 and PTD56 revealed that all the bladder in human mesenchymal stem cell (hMSCs) and two control groups was hyperreflexic type (67-83% within each case), and there was no difference of micturition frequency and pressure, the chance of detrusor contraction without micturition, and bladder volume among hMSC group and two control groups (Table 1)
ELISA study When comparing the protein levels of brain derived neurotrophic factor (BDNF) and NT-3 among two control groups and hMSC group, there was no significant difference of the concentration of BDNF and NT-3 in thoracic and lumbar spinal cords and bladder between hMSC and control groups at PTD28 and PTD56 (Fig. 2)
Summary
Mesenchymal stem cells are widely used for transplantation into the injured spinal cord in vivo model and for safety, many human clinical trials are continuing to promote improvements of motor and sensory functions after spinal cord injury. Neurogenic bladder following spinal cord injury is the main problem decreasing the quality of life for patients with spinal cord injury, but there are no clear data using stem cell transplantation for the improvement of neurogenic bladder for in vivo studies and the clinical setting. The present goals of the management of neurogenic bladder in patients with spinal cord injury are the preservation of the renal function and increasing the quality of life for patients by minimizing complications [1], but the restoration of bladder function after spinal cord injury has proven to be difficult to achieve because techniques in axonal regeneration and tissue repair remain quite limited until now. Clinical trials of autologous hMSC transplantation were performed on acute and chronic patients with spinal cord injury [13,14,15,16] and the safety and some clinical improvements for human were reported but the exact mechanism of hMSCs on the functional recovery are still unclear [17]
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