Stem cell therapy and curcumin synergistically enhance recovery from spinal cord injury.
Stem cell therapy and curcumin synergistically enhance recovery from spinal cord injury.
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DOI：
10.1371/journal.pone.0088916
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Jhanwar-Uniyal M
中科院分区：
文献类型：
--
作者：
Ormond DR;Shannon C;Oppenheim J;Zeman R;Das K;Murali R;Jhanwar-Uniyal M
急性创伤性脊髓损伤（SCI）的特点是局部细胞因子和促炎物质的产生增加，这些物质会诱导神经胶质增生并阻止神经再生。干细胞移植是一种有前景的脊髓损伤治疗策略。为了促进功能恢复，我们单独采用干细胞疗法或与姜黄素联合使用，姜黄素是姜黄 (Curcuma longa) 中天然存在的抗炎成分，可有效抑制 NF-κB。使用重量下降装置（在 12.5 或 25 毫米距离上施加 10 克，分别代表中度或重度 SCI）对 Sprague-Dawley 大鼠进行椎板切除术 (T9-10) 后的脊髓挫伤。从室下区 (SVZ) 分离神经干细胞 (NSC)，并在有或没有姜黄素治疗的情况下移植到损伤部位。通过 BBB 评分和 SCI 后 6 周内测量的体重增加来评估功能恢复情况。研究结束时，比目鱼肌的质量与 BBB 评分和体重相关。干细胞治疗改善了中度 SCI 的恢复，但对重度 SCI 后的恢复效果有限。姜黄素在体外刺激 NSC 增殖，并与干细胞治疗相结合，诱导严重 SCI 的深度恢复，表现为功能性运动恢复的改善、体重和比目鱼肌质量的增加。这些发现表明，姜黄素与干细胞疗法相结合可协同改善严重 SCI 的恢复。此外，我们的结果表明姜黄素的作用超出了其已知的抗炎特性，还可以调节干细胞增殖。
Acute traumatic spinal cord injury (SCI) is marked by the enhanced production of local cytokines and pro-inflammatory substances that induce gliosis and prevent reinnervation. The transplantation of stem cells is a promising treatment strategy for SCI. In order to facilitate functional recovery, we employed stem cell therapy alone or in combination with curcumin, a naturally-occurring anti-inflammatory component of turmeric (Curcuma longa), which potently inhibits NF-κB. Spinal cord contusion following laminectomy (T9–10) was performed using a weight drop apparatus (10 g over a 12.5 or 25 mm distance, representing moderate or severe SCI, respectively) in Sprague-Dawley rats. Neural stem cells (NSC) were isolated from subventricular zone (SVZ) and transplanted at the site of injury with or without curcumin treatment. Functional recovery was assessed by BBB score and body weight gain measured up to 6 weeks following SCI. At the conclusion of the study, the mass of soleus muscle was correlated with BBB score and body weight. Stem cell therapy improved recovery from moderate SCI, however, it had a limited effect on recovery after severe SCI. Curcumin stimulated NSC proliferation in vitro, and in combination with stem cell therapy, induced profound recovery from severe SCI as evidenced by improved functional locomotor recovery, increased body weight, and soleus muscle mass. These findings demonstrate that curcumin in conjunction with stem cell therapy synergistically improves recovery from severe SCI. Furthermore, our results indicate that the effect of curcumin extends beyond its known anti-inflammatory properties to the regulation of stem cell proliferation.
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