Left ventricular transplantation of human umbilical cord blood mononuclear cells in the treatment of cerebral hemorrhage in rats: micro PET-CT evaluation and therapeutic mechanism

doi:10.3969/j.issn.2095-4344.0928

Abstract

Abstract:

BACKGROUND: In recent years, new stem cell transplantation therapies for cerebral hemorrhage have emerged, but little is reported on human umbilical cord blood mononuclear cells (HUCB-MNCs), especially on micro PET-CT evaluation of HUCB-MNCs effects.
OBJECTIVE: To evaluate the therapeutic effect of HUCB-MNCs in a rat model of cerebral hemorrhage by Longa and micro PET-CT and to explore the therapeutic mechanism.
METHODS: Models of cerebral hemorrhage were established in rats using secondary blood injection/needle retraction method. The rats in the experimental group were treated with HUCB-MNCs via left ventricular transplantation, and those in the control group received no treatment. Before and after transplantation (3, 7, 14, 21 days), the rats in the two groups were evaluated using Longa 5 scores and micro PET-CT images. ELISA was used to detect the level of angiotensin 1 in the brain homogenate.
RESULTS AND CONCLUSION: Longa 5 scores in the two groups were gradually decreased with time (P < 0.05). Compared with the control group, the Longa 5 scores in the experimental group decreased more significantly (P < 0.05). The standard absorption value (SUV%) in the center of hematoma and perihematomal region increased gradually in the two groups at 7, 14, 21 days after transplantation, but it was significantly higher in the experimental group than the control group (P < 0.05). The volume of hematoma and surrounding tissues was gradually reduced in the two groups, especially in the experimental group, at 7, 14, 21 days after transplantation (P < 0.05). The level of angiotensin 1 in the control group increased gradually with time (P < 0.05), while the level of angiotensin 1 in the experimental group gradually increased, peaked at 14 days and then reduced at 21 days after transplantation (P < 0.05). The level of angiotensin 1 was higher in the experimental group than the control group (P < 0.05). Overall, these findings reveal that HUCB-MNCs via left ventricular transplantation can improve neurologic function of rats, reduce hematoma, recover hematoma metabolism, and increase the level of angiotensin 1 in the rat brain, indicating that HUCB-MNCs transplantation can promote the repair of cerebral hemorrhage through neo-angiogenesis regulation.

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: Cerebral Hemorrhage, Cord Blood Stem Cell Transplantation, Tissue Engineering

CLC Number:

R394.2

Wei Lin-huan, Yao Xing-yu, Zhang Guo-hua, Yang Li-min, Li Jian-bo, Liu Jie, Jin Na, Duan Rui. Left ventricular transplantation of human umbilical cord blood mononuclear cells in the treatment of cerebral hemorrhage in rats: micro PET-CT evaluation and therapeutic mechanism[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(25): 4059-4064.

Figures/Tables 2

2.1 大鼠脑出血模型建立情况大鼠均在造模后三四个小时内意识转清，并出现神经功能缺损症状(图1)，PET-CT扫描显示右侧尾状核区脑出血(图2)。在56只脑出血模型中，6只大鼠造模失败，50只大鼠造模成功。 2.2 不同时间点大鼠神经Longa5级评分实验组和对照组各时间点Longa5级评分均随时间逐渐降低，各时间点差异有显著性意义(F实验组=28.08，P实验组=0.000 3；F对照组=13.83，P对照组=0.000 1)；实验组较对照组Longa5级评分降低更明显，除移植前及移植后第3天外，各时间点两组大鼠Longa5级评分差异均有显著性意义(P < 0.05)，见表1。 2.3 microPET-CT扫描及数据分析 2.3.1 两组大鼠移植前后不同时间点PET-CT血肿图像比较见图3。移植后第3天两组大鼠血肿体积均增大，第7，14，21天两组血肿体积均逐渐减小，移植后相同时间点实验组大鼠血肿体积均小于对照组大鼠。 2.3.2 两组大鼠移植前后不同时间点PET-CT血肿中心代谢(SUV%)情况比较实验组及对照组血肿中心代谢有随时间变化的趋势，均表现为移植后第3天较移植前血肿中心代谢水平降低，移植后第7，14，21天血肿中心代谢水平逐渐升高，各时间点差异有显著性意义(F实验组=18.71， P实验组=0.000 2；F对照组=4.57，P对照组=0.009)；实验组较对照组血肿中心代谢水平高，除移植前及移植后第3天外，各时间点两组大鼠血肿中心代谢水平差异均有显著性意义(P < 0.05)，见表2。 2.3.3 两组大鼠移植前后不同时间点PET-CT血肿周围代谢(SUV%)水平比较实验组及对照组血肿周围代谢水平有随时间逐渐升高的趋势，各时间点差异有显著性意义(F实验组=19.02，P实验组=0.000 3；F对照组=7.69，P对照组=0.001)。实验组较对照组血肿周围代谢水平高，除移植前外，各时间点两组大鼠血肿周围代谢水平差异均有显著性意义(P < 0.05)，见表3。 2.3.4 两组大鼠移植前后不同时间点PET-CT血肿及周围体积变化比较实验组及对照组大鼠血肿及周围体积有随时间变化的趋势，表现为移植后第3天较移植前血肿及周围体积更大，移植后第7，14，21天血肿及周围体积逐渐减小，各时间点差异有显著性意义(F实验组=21.45，P实验组=0.000 3；F对照组=30.10，P对照组=0.000 1)；实验组较对照组血肿及周围体积更小，除移植前外，各时间点两组大鼠血肿及周围体积差异均有显著性意义(P < 0.05)，见表4。 2.4 ELISA法测定脑匀浆中血管紧张素1水平对照组组内各时间点血管紧张素1水平随时间变化逐渐升高，各时间点差异有显著性意义(F对照组=55.19，P对照组=0.000 9)；实验组组内各时间点血管紧张素1水平随时间变化逐渐升高，移植后14 d达峰值，移植后21 d又下降，各时间点差异有显著性意义(F实验组=23.05，P实验组=0.000 3)；实验组较对照组血管紧张素1水平更高，除移植前及移植后第3天外，各时间点两组大鼠血管紧张素1水平差异均有显著性意义(P < 0.05)，见表5。"

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