Different doses of human umbilical cord mesenchymal stem cells improve learning and memory ability of dementia rats

doi:10.3969/j.issn.2095-4344.2016.50.011

Abstract

Abstract:

BACKGROUND: To delay the onset of Alzheimer’s disease, transplantation of viable and well-differentiated stem cells is expected to repair neural tissue, which has been an issue of concern.
OBJECTIVE: To explore the effects of different doses of human umbilical cord mesenchymal stem cells (hUCMSCs) on learning and memory ability of Alzheimer’s disease rats.
METHODS: Fifty Sprague-Dawley rats, 7 months of age, were randomized into normal, model, high-, middle- and low-dose hUCMSCs groups (n=10 per group). Rats in model and UCMSCs groups were used to make Alzheimer’s disease animals through intraperitoneal injection of 150 mg/kg D-galactose for 90 days, and rats in the normal group were given intraperitoneal injection of normal saline for 90 days. In the three hUCMSCs group, passage 3 hUCMSCs at doses of 1×10⁵/0.2 mL/20 g, 5×10⁵/0.2 mL/20 g, and 1×10⁶/0.2 mL/20 g were injected via the tail vein, respectively. Forty-five days after cell transplantation, Morris water maze test was used to detect rat’s learning and memory abilities, and hematoxylin-eosin staining was used to observe pathological changes of the rat hippocampal CA1 region.
RESULTS AND CONCLUSION: Compared with the normal group, the rats in the model group showed significant reduction in the ability of learning and memory. Compared with the model group, the escape latency was significantly shortened in the middle-dose hUCMSCs group (P < 0.05), while the number of passing times through the platform was increased significantly (P < 0.05). In the model group, the cells in the hippocampal CA1 region were arranged irregularly with unclear nucleoli and a part of cells were concentrated and deeply stained. In the middle-dose hUCMSCs group, the cells in the hippocampal CA1 region were arranged regularly with clear nucleoli, and only individual cells were stained deeply. These findings indicate that middle-dose hUCMSCs transplantation can improve the learning and memory abilities of Alzheimer’s rats.

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: Umbilical Cord, Mesenchymal Stem Cell Transplantation, Alzheimer Disease, Tissue Engineering

CLC Number:

R394.2

Zhou Jun, Zhou De-sheng . Different doses of human umbilical cord mesenchymal stem cells improve learning and memory ability of dementia rats[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(50): 7524-7529.

Figures/Tables 1

References

[1] 陆盈盈.小鼠老年痴呆模型的建立及甘丙肤的表达研究[D].上海:华东师范大学,2007.

[2] 赵海善.老年期痴呆病因及发病机制的研究进展[J].老年医学与保健,2006,12(1):56-57.

[3] 许冠思.运动对老年痴呆症的影响[J].中国误诊学杂志, 2011,11(1): 91.

[4] 王芳媛.体育运动对老年痴呆症的预防及运动处方的制定[J].辽宁体育科技,2005,27(2):42-43.

[5] 韩璇,王永丽,问慧娟,等.灯盏花抗老年痴呆作用的研究进展[J].医学研究与教育,2011,28(1):76-78.

[6] 肖志杰,李秋香,程灶火,等. 老年精神分裂症和Alzheimer氏病患者认知功能的对照研究[J].中国临床心理学杂志, 2001,9(3):164-167.

[7] 沈阳,陈宇,傅洁瑜,等. 老年痴呆症的分子机制[J].生命科学,2014,26(6):550-559.

[8] 何洋,周煜东.老年痴呆症中神经递质释放异常的机理[J].生命科学,2014,26(1):27-34.

[9] GUo ZY,Sun X,Xu XL,et al.Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms. Neural Regen Res. 2015;10(4): 651-658.

[10] 周会芳,张密霞,高丽,等.脐带间充质干细胞移植对老年痴呆小鼠 SAMP8学习记忆的影响[J].世界中医药,2015, 10(9):1383-1386.

[11] 崔渊博,马珊珊,姚宁,等.人脐带间充质干细胞移植对老年痴呆小鼠脑、肝组织中衰老相关基因表达的影响[J].郑州大学学报,2015,50(1):25-29.

[12] 王毅鹏,金醒昉.人脐带间充质干细胞移植治疗血管性痴呆的研究进展[J].中国老年学杂志,2015,35(3):827-829.

[13] Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005; 366(9503):2112-2117.

[14] 田金洲,时晶,苗迎春,等.阿尔茨海默病的流行病学特点及其对公共卫生观念的影响[J].湖北中医学院学报,2009, 11(1):3-7.

[15] 尹兆宝,王健,周如倩,等.补肾方对老年性痴呆大鼠学习记忆和细胞因子的影响[J].中国老年学杂志,2000,20(1): 33-34.

[16] 罗焕敏,陈子晟.一种新的老年痴呆动物模型[J].中国老年学杂志,2003,23(3):179-182.

[17] 任榕娜,陈新民.避暗及迷宫实验研究锌缺乏及锌过量对大鼠学习记忆的影响[J].现代预防医学,1997,24(1): 61-62.

[18] 丛伟红,刘建勋.老年性痴呆动物模型研究进展[J].中国药理学通报,2003,19(5):497-501.

[19] 蒋洁,张雪梅,张建湘.脐带间充质干细胞研究进展[J].广东医学,2010,31(14):1885 -1887.

[20] 程欣,罗焕敏.干细胞移植治疗阿尔茨海默病的研究进展[J].基础医学与临床,2011,31(2): 218-221.

[21] 杨柏灿,叶善龙.Alzheimer痴呆的中医病因病机探析[J].中国中医基础医学杂志,1999,5(1):51-54.

[22] 马宜明,李俊,金涌.中医药关于老年性痴呆的发病机制及治疗进展[J].安徽医药,2002,6(4):3-5.

[23] 杨文明,韩明向.老年性痴呆病机探讨[J]. 中国中医药信息杂志,2001,8(4):11-13.

[24] 陆明霞,于建春,于涛,等.中医学论老年性痴呆[J].中国中医基础医学杂志,2003,9(6):44-46.

[25] 赵淑梅,岳启安,左凤英,等.呆聪液对老龄大鼠痴呆模型免疫功能的影响[J].淮坊医学院学报,2000,22(1): 11-13.

[26] 刘一凡,石学敏,韩景献,等.针刺对快速老化脑萎缩模型小鼠脑抗氧化酶活性的影响[J].中国针灸,2002,22(5): 327-330.

[27] 许婷婷,李军,周艳华,等.人脐带间充质干细胞对小鼠衰老进程中骨髓细胞集落生成的影响[J].暨南大学学报,2009, 30(6): 614-618.

[28] Liu J,Ma YX,Tian SM,et al.T cells promote the regeneration of neural precursor cells in the hippocampus of Alzheimer’s disease mice. Neural Regen Res. 2014;9 (16): 1541-1547.

[29] Chan YC, Hosoda K, Tsai CJ, et al. Favorable effects of tea on reducing the cognitive deficits and brain morphological changes in senescence-accelerated mice. J Nutr Sci Vitaminol (Tokyo). 2006;52(4):266-273.

[30] Liao JW, Hsu CK, Wang MF, et al. Beneficial effect of Toona sinensis Roemor on improving cognitive performance and brain degeneration in senescence-accelerated mice. Br J Nutr. 2006;96(2): 400-407.

[31] 李莹,王景周.人脐血干细胞海马CA1区移植及GM1腹腔注射治疗大鼠血管性痴呆[J].第三军医大学学报,2008, 30(12):1154-1158.

[32] Liao W, Xie J, Zhong J, et al. Therapeutic effect of human umbilical cord multipotent mesenchymal stromal cells in a rat model of stroke. Transplantation. 2009;87(3):350-359.

[33] Ding DC, Shyu WC, Chiang MF, et al. Enhancement of neuroplasticity through upregulation of beta1-integrin in human umbilical cord-derived stromal cell implanted stroke model. Neurobiol Dis. 2007;27(3):339-353.

[34] Liao W, Zhong J, Yu J, et al. Therapeutic benefit of human umbilical cord derived mesenchymal stromal cells in intracerebral hemorrhage rat: implications of anti-inflammation and angiogenesis. Cell Physiol Biochem. 2009;24(3-4):307-316.