Iijima Keiya, Kurachi Masashi, Shibasaki Koji, Naruse Masae, Puentes Sandra, Imai Hideaki, Yoshimoto Yuhei, Mikuni Masahiko, Ishizaki Yasuki
Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
J Neurochem. 2015 Nov;135(3):539-50. doi: 10.1111/jnc.13262. Epub 2015 Sep 17.
We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases.
我们之前的研究表明,脑微血管内皮细胞(MVECs)移植能极大地促进由内皮素-1注射诱导的内囊(IC)白质梗死中的髓鞘再生,并改善行为结果。在本研究中,我们使用间歇性磁共振成像检查了MVEC移植对梗死体积的影响,并通过组织化学方法研究了其对少突胶质细胞谱系细胞行为的影响。我们的体内研究结果表明,MVEC移植减少了IC中的梗死体积以及少突胶质细胞前体细胞(OPCs)的凋亡死亡。这些结果表明,MVECs对OPCs具有存活作用,且这种作用可能有助于白质梗死的恢复。培养的MVECs的条件培养基可减少培养的OPCs的凋亡,而培养的成纤维细胞的条件培养基则未显示出这种作用。这些结果提示,移植的MVECs可能通过释放防止其凋亡死亡的体液因子来增加OPCs的数量。鉴定此类体液因子可能会带来针对缺血性脱髓鞘疾病的新治疗策略。