中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (1): 65-69.doi: 10.3969/j.issn.2095-4344.0412

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

人胎盘间充质干细胞移植对脑梗死大鼠的神经保护作用

陈东平,侯淑红,郭 元,胡职舟,胡小红,陈衍贵,陈明生   

  1. 福建医科大学附属龙岩第一医院神经内科,福建省龙岩市 364000
  • 修回日期:2017-09-06 出版日期:2018-01-08 发布日期:2018-01-08
  • 通讯作者: 侯淑红,硕士,主治医师,福建医科大学附属龙岩第一医院,福建省龙岩市 364000
  • 作者简介:陈东平,男,1981年生,福建省漳平市人,汉族,2009年福建医科大学毕业,博士,副主任医师,主要从事脑血管病研究。 并列第一作者:侯淑红,硕士,主治医师,主要从事脑血管病研究。
  • 基金资助:

    福建省卫生计生委青年科研课题(2015-1-104)

Human placenta-derived mesenchymal stem cell transplantation provides neuroprotection against cerebral infarction in rats

Chen Dong-ping, Hou Shu-hong, Guo Yuan, Hu Zhi-zhou, Hu Xiao-hong, Chen Yan-gui, Chen Ming-sheng   

  1. Department of Neurology, the Affiliated Longyan First Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China
  • Revised:2017-09-06 Online:2018-01-08 Published:2018-01-08
  • Contact: Hou Shu-hong, Department of Neurology, the Affiliated Longyan First Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China
  • About author:Chen Dong-ping, M.D., Associate chief physician, Department of Neurology, the Affiliated Longyan First Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China. Hou Shu-hong, Master, Attending physician, Department of Neurology, the Affiliated Longyan First Hospital of Fujian Medical University, Longyan 364000, Fujian Province, China. Chen Dong-ping and Hou Shu-hong contributed equally to this work.
  • Supported by:

    Youth Research Foundation of Fujian Health and Family Planning Commission, No. 2015-1-104

摘要:

文章快速阅读:

文题释义:
胎盘间充质干细胞:
一种具有自我复制能力的多潜能干细胞。在一定条件下,其可分化成多种功能细胞。在胚胎发育中来源于中胚层。在组织损伤引起的特殊信号作用下,其可迁移到受损部位,在局部聚集增殖,依据不同的损伤信号沿着不同途径分化。
干细胞移植治疗脑梗死:干细胞在体内具有一定的趋向性,发生脑梗死后干细胞向脑梗死区域迁移。运用干细胞技术,即从人体分离纯化少量干细胞,经体外培养、定向诱导、基因修饰,再将其移植到患者的脑内,可达到促进受损脑组织修复及重建的目的。

 

摘要
背景:
骨髓间充质干细胞可促进脑梗死后的神经功能修复,但其在骨髓中含量极低,难以分离和纯化。
目的:探讨人胎盘间充质干细胞对脑梗死大鼠的神经保护作用及机制。
方法:取成功建立大脑中动脉阻塞脑梗死模型的120只SD大鼠,随机分成治疗组和对照组,各60只,治疗组经尾静脉移植人胎盘间充质干细胞,对照组注射相同剂量的PBS。治疗后第1,3,7,14天,进行神经功能缺损评分;治疗后第14天,TTC染色法计算脑梗死体积,抗人特异的线粒体抗体免疫组化染色计算迁移并存活的人胎盘间充质干细胞数量,TUNEL染色检测脑缺血区细胞凋亡情况;治疗后第3,7,14天,用ELISA法检测脑缺血区脑源性神经生长因子、血管内皮生长因子和肝细胞生长因子水平。
结果与结论:①治疗后第1,3,7,14天,治疗组的改良神经功能缺损评分显著低于对照组(P < 0.05);②治疗后第14天,治疗组脑梗死体积显著小于对照组(P < 0.05),在治疗组脑缺血区只发现少数移植的干细胞,治疗组缺血脑组织TUNEL阳性细胞显著少于对照组(P < 0.05);③治疗后第3,14天,治疗组缺血脑组织脑源性神经生长因子表达水平显著高于对照组(P < 0.05),治疗后第7,14天,治疗组缺血脑组织血管内皮生长因子表达水平显著高于对照组(P < 0.05),治疗后第7天,治疗组缺血脑组织肝细胞生长因子表达水平显著高于对照组(P < 0.05);④结果提示,人胎盘间充质干细胞对脑梗死具有神经保护作用,其可使脑缺血区细胞因子表达增加,细胞凋亡减少。

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程
ORCID:
0000-0002-0399-1212(陈东平)

关键词: 干细胞, 移植, 脑梗死, 胎盘间充质干细胞, 神经保护, 细胞因子

Abstract:

BACKGROUND: Bone marrow mesenchymal stem cells improve neurological functional recovery from cerebral infarction, but they are a rare population in the bone marrow with difficulty in cell separation and purification.
OBJECTIVE: To investigate the neuroprotective effects and the potential mechanisms of human placenta-derived mesenchymal stem cell transplantation for cerebral infarction in rats.
METHODS: Totally 120 rats subjected to middle cerebral artery occlusion were randomized into treatment group and control (n=60 per group). The rats were intravenously treated with human placenta-derived mesenchymal stem cells in the treatment group or the phosphate buffer saline in the control group. Then, a modified neurological severity score was assessed at 1, 3, 7, 14 days post transplantation, and measurement of infarct volume in the ischemic brain was performed using 2,3,5-triphenyltetrazolium chloride staining at 14 days post transplantation. The anti-human specific immunostain for mitochondria in the ischemic brain was performed and the mitochondria-positive cells were counted; TUNEL immunostaining was performed and TUNEL positive cells were counted. ELISA assays for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also performed in the ischemic brain.
RESULTS AND CONCLUSION: At 1, 3, 7 and 14 days after treatment, the modified neurological severity score in the treatment group was significantly lower than that in the control group (P < 0.05). At 14 days after treatment, the infarct volume in the treatment group was significantly lower than that in the control group (P < 0.05), only few mitochondria-positive cells were present in the ischemic brain, and the number of TUNEL positive cells in the treatment group was significantly less than that in the control group (P < 0.05). At 3 and 14 days after treatment, BDNF expression levels in the treatment group were significantly higher than those in the control group (P < 0.05). At 7 and 14 days after treatment, VEGF expression levels in the treatment group were significantly higher than those in the control (P < 0.05). At 7 days after treatment, HGF expression level in the treatment group was significantly higher than that in the control group (P < 0.05). To conclude, intravenous administration of human placenta-derived mesenchymal stem cells can promote neuroprotective effects against cerebral infarction. These effects may be related to the increase of BDNF, VEGF and HGF expression and the decrease of apoptosis in the ischemic brain.

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

Key words: Brain Infarction, Placenta, Mesenchymal Stem Cell Transplantation, Cytokines, Tissue Engineering

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