中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (13): 1201-1209.doi: 10.3969/j.issn.1673-5374.2013.13.005

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

骨髓再生细胞是治疗脑缺血更为优越的种子细胞?

  

  • 收稿日期:2012-12-30 修回日期:2013-03-27 出版日期:2013-05-05 发布日期:2013-05-05

Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?

Yi Li1, Xuming Hua1, Fang Hua2, Wenwei Mao3, Liang Wan1, Shiting Li1   

  1. 1 Department of Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
    2 Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA
    3 Laboratory of Microbiology and Biochemical Pharmaceutics, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
  • Received:2012-12-30 Revised:2013-03-27 Online:2013-05-05 Published:2013-05-05
  • Contact: Shiting Li, M.D., Ph.D., Chief physician, Department of Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China, lsting66@163.com.

摘要:

目前研究认为,骨髓细胞治疗缺血性脑损伤的可能机制是通过分泌大量营养因子发挥治疗作用,骨髓再生细胞具有较强分泌营养因子能力。鉴于此,采集大鼠股骨和胫骨的骨髓细胞制备骨髓细胞,采集经过尾静脉注射5-氟尿嘧啶脱氧核苷酸后第7天的大鼠股骨和胫骨的骨髓细胞制备骨髓再生细胞,将上述两种细胞分别尾静脉注射于局灶性脑缺血模型大鼠。免疫组织学染色和RT-PCR检测发现,骨髓细胞和骨髓再生细胞均在移植后迁移到大鼠缺血区--皮质和纹状体梗死区并存活,并可促进大鼠缺血半暗带区--皮质和纹状体梗死中心周围缺血边缘区的血管内皮细胞生长因子mRNA的表达,促进缺血血管再生、缩小梗死灶体积并促进神经功能恢复,在上述所有疗效中骨髓再生细胞作用最强。说明骨髓再生细胞可作为更为优越的种子细胞诱导缺血脑组织神经和血管再生,促进血管再生因子分泌可能是其主要的作用机制。

关键词: 神经再生, 脑损伤, 脑缺血, 种子细胞, 骨髓, 移植, 骨髓细胞, 骨髓再生细胞, 血管再生因子

Abstract:

Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohistological staining and reverse transcription-PCR detection showed that transplanted bone marrow cells and bone marrow regenerative cells could migrate and survive in the ischemic regions, such as the cortical and striatal infarction zone. These cells promote vascular endothelial cell growth factor mRNA expression in the ischemic marginal zone surrounding the ischemic penumbra of the cortical and striatal infarction zone, and have great advantages in promoting the recovery of neurological function, reducing infarct size and promoting angiogenesis. Bone marrow regenerative cells exhibited stronger neuroprotective effects than bone marrow cells. Our experimental findings indicate that bone marrow regenerative cells are preferable over bone marrow cells for cell therapy for neural regeneration after cerebral ischemia. Their neuroprotective effect is largely due to their ability to induce the secretion of factors that promote vascular regeneration, such as vascular endothelial growth factor.

Key words: neural regeneration, brain injury, cerebral ischemia, seed cells, bone marrow, transplantation, bone marrow cells, bone marrow regenerative cells, vascular regeneration factor, brain, neuroregeneration