JCI:脊髓损伤新疗法

2010-08-20 文章来源:J Clin Invest. doi:10.1172/JCI42957 点击量:2022   我要说

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      8月17日,日本研究人员在美国《临床检查杂志》(JCI)月刊上发表论文说,他们在动物实验中,利用神经干细胞和抗癫痫药物,有效地使脊髓损伤的实验鼠神经细胞获得再生,恢复了行走能力。

      在此前的动物实验中,日本奈良尖端科学技术大学院大学与鹿儿岛大学的研究人员曾尝试通过给实验鼠移植诱导多功能干细胞(iPS细胞)的方法修复受损神经,但是干细胞发育为神经细胞的概率只有不到1%。而且如果是重症,则很难恢复。

      后来,研究人员发现,抗癫痫药物丙戊酸能够改变神经干细胞的基因结构,从而高效分化生成神经细胞。

      他们于是给后肢因脊髓损伤而失去知觉的实验鼠移植了从其他实验鼠胎儿的大脑采集的神经干细胞,并且连续一周给移植了神经干细胞的实验鼠注射丙戊酸。6周后,21只实验鼠中有15只重新能够行走,虽然腿脚还不怎么灵便;其余6只的症状也大为改善。

      如果剔除移植的干细胞发育成的神经细胞,则实验鼠会再次失去行走能力,这证明移植的干细胞发挥了直接效果,使实验鼠重建了神经网络。而移植干细胞后接着注射丙戊酸,可使干细胞发育成神经细胞的概率增加到约20%。

      因交通事故或跌落等导致脊髓损伤,往往会使下半身失去知觉,以往治疗非常困难,新方法使治疗脊髓损伤向前迈进了一大步。

      研究人员将这种手法命名为"HINT"法,他们今后将在灵长类动物身上进行实验,希望能早日应用于临床治疗。

      研究小组的中岛钦一教授指出:“这是世界上组合使用干细胞和抗癫痫药物的首次尝试。这种方法不仅适用于脊髓损伤,也许还可以用于治疗伴随着神经损伤的脑中风帕金森氏症、阿尔茨海默氏症等。”

原文出处:

J Clin Invest. doi:10.1172/JCI42957.

Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury
Masahiko Abematsu1,2, Keita Tsujimura1, Mariko Yamano3, Michiko Saito4, Kenji Kohno4, Jun Kohyama1, Masakazu Namihira1, Setsuro Komiya2 and Kinichi Nakashima1

1Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
2Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
3Department of Comprehensive Rehabilitation, Osaka Prefecture University, Habikino, Japan.
4Laboratory of Molecular and Cell Genetics, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.

The body’s capacity to restore damaged neural networks in the injured CNS is severely limited. Although various treatment regimens can partially alleviate spinal cord injury (SCI), the mechanisms responsible for symptomatic improvement remain elusive. Here, using a mouse model of SCI, we have shown that transplantation of neural stem cells (NSCs) together with administration of valproic acid (VPA), a known antiepileptic and histone deacetylase inhibitor, dramatically enhanced the restoration of hind limb function. VPA treatment promoted the differentiation of transplanted NSCs into neurons rather than glial cells. Transsynaptic anterograde corticospinal tract tracing revealed that transplant-derived neurons reconstructed broken neuronal circuits, and electron microscopic analysis revealed that the transplant-derived neurons both received and sent synaptic connections to endogenous neurons. Ablation of the transplanted cells abolished the recovery of hind limb motor function, confirming that NSC transplantation directly contributed to restored motor function. These findings raise the possibility that epigenetic status in transplanted NSCs can be manipulated to provide effective treatment for SCI.

来源:生物谷

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