Department of Rehabilitation Medicine, College of Medicine, Dankook University, Cheonan, Korea.
BMC Neurosci. 2010 Sep 16;11:119. doi: 10.1186/1471-2202-11-119.
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. 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.
Modified 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.
hMSC 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.
间充质干细胞被广泛用于体内损伤脊髓移植,为了安全起见,许多人体临床试验正在继续促进脊髓损伤后运动和感觉功能的改善。然而,这些改善的确切机制仍未确定。脊髓损伤后的神经原性膀胱是降低脊髓损伤患者生活质量的主要问题,但在体内研究和临床环境中,没有使用干细胞移植改善神经原性膀胱的确切数据。本研究的目的是描述人骨髓间充质干细胞(hMSC)移植对大鼠脊髓挫伤后神经原性膀胱和受损后肢功能恢复的影响,以及神经营养因子如脑源性神经营养因子(BDNF)和神经营养因子-3(NT-3)与膀胱和后肢功能的关系。
使用 MASCIS 撞击器对 Sprague-Dawley 大鼠的胸段脊髓进行改良中度挫伤,在损伤后 9 天,将 hMSC、人成纤维细胞或磷酸盐缓冲液分别移植到损伤的脊髓中,用于 hMSC 和两个对照组。梯级试验显示,hMSC 组后肢功能恢复较对照组更快,但 hMSC 组和两个对照组的 Basso、Beattie 和 Bresnahan 评分和耦合评分无显著差异。两组均未改善神经原性膀胱。hMSC 组 ED1 阳性巨噬细胞明显少于两个对照组,但 ELISA 和 RT-PCR 研究显示,无论实验持续时间如何,hMSC 组和两个对照组的脊髓和膀胱中的 BDNF 和 NT-3 水平均无差异。
hMSC 移植可有效减轻大鼠脊髓挫伤后的炎症反应,但不足以恢复运动和膀胱功能障碍。hMSC 移植后 28 天和 56 天,脊髓和膀胱中的 BDNF 和 NT-3 水平均未增加。