Ginkgo-damole injection combined with bone marrow mesenchymal stem cell transplantation improves neurologic recovery from cerebral infarction

doi:10.3969/j.issn.2095-4344.2015.50.013

Abstract

Abstract:

BACKGROUND: Reconstruction of damaged brain tissue through cell transplantation has become a new way to treat cerebral infarction. In recent years, bone marrow mesenchymal stem cells have become the new darling in cell transplantation therapy.
OBJECTIVE: To investigate the effect of ginkgo-damole injection combined with bone marrow mesenchymal stem cell transplantation to improve the neurological function of acute cerebral infarction rats and its mechanism.
METHODS: Animal models of middle cerebral artery occlusion were made in rats using suture method, and then 60 rat models were randomly divided into control group, cell transplantation group and combination group. The control group was given intravenous injection of PBS via the tail vein; the cell transplantation group was given intravenous injection of bone marrow mesenchymal stem cell suspension (2.5×109/L) via the tail vein; the combination group was given intravenous injection of bone marrow mesenchymal stem cell suspension (2.5×109/L) and ginkgo-damole injection (2 mL/kg, once a day, totally 5 days) via the tail vein. Modified
neurological severity scores were recorded at 1, 3 days and 1, 2 weeks after transplantation. At 2 weeks after transplantation, expressions of brain-derived neurotrophic factor and growth associated protein 43 in the brain were detected using RT-PCR; cell apoptosis detected using MTT assay; BrdU positive cells counted using immunohistochemistry method.
RESULTS AND CONCLUSION: There were no differences in the modified neurologic severity scores among the three groups at 1, 3 days after transplantation (P > 0.05), but the modified neurological severity scores in the combination group were lower than those in the cell transplantation group and control group at 1, 2 weeks after transplantation (P < 0.05). The expressions of brain-derived neurotrophic factor and growth associated protein 43 in the brain were significantly higher in the combination group than the other two groups at 2 weeks after transplantation (P < 0.05); compared with the other two groups, the number of apoptotic cells was less but the number of BrdU positive cells was higher in the combination group (P < 0.05). These findings indicate that the combination of ginkgo-damole injection and bone marrow mesenchymal stem cell transplantation can increase the expressions of brain-derived neurotrophic factor and growth associated protein 43 in the brain, inhibit cell apoptosis and improve neurological function in rats with cerebral infarction.

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

CLC Number:

R394.2

Yang Chao-yang. Ginkgo-damole injection combined with bone marrow mesenchymal stem cell transplantation improves neurologic recovery from cerebral infarction[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(50): 8108-8113.

Figures/Tables 6

References

[1] Zheng W, Honmou O, Miyata K, et al. Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia. Brain Res. 2010;1310:8-16.

[2] Akiyama K, You YO, Yamaza T, et al. Characterization of bone marrow derived mesenchymal stem cells in suspension. Stem Cell Res Ther. 2012;3(5):40.

[3] Yip HK, Chang LT, Chang WN, et al. Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke. 2008;39(1):69-74.

[4] 杨志华,徐凤霞,彭烈标,等.BMSCs移植后梗死灶周围及室管膜下区神经元增殖促进大鼠神经功能恢复[J].中华神经医学杂志, 2014,13(4):348-352.

[5] Barbosa da Fonseca LM, Gutfilen B, Rosado de Castro PH, et al. Migration and homing of bone-marrow mononuclear cells in chronic ischemic stroke after intra-arterial injection. Exp Neurol. 2010;221(1):122-128.

[6] Li Z, Tian X, Yuan Y, et al. Effect of cell culture using chitosan membranes on stemness marker genes in mesenchymal stem cells. Mol Med Rep. 2013;7(6):1945-1949.

[7] Hokari M, Kuroda S, Chiba Y, et al. Synergistic effects of granulocyte-colony stimulating factor on bone marrow stromal cell transplantation for mice cerebral infarct. Cytokine. 2009; 46(2):260-266.

[8] Kawabori M, Kuroda S, Ito M, et al. Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct. Neuropathology. 2013;33(2):140-148.

[9] 吴涛,安锐,张斌青,等.131I-FIAU/TK报告基因系统监测大鼠脑梗死模型中移植细胞的研究[J].中华核医学杂志,2011,31(5): 301-305.

[10] Wakabayashi K, Nagai A, Sheikh AM, et al. Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model. J Neurosci Res. 2010;88(5):1017-1025.

[11] Komatsu K, Honmou O, Suzuki J, et al. Therapeutic time window of mesenchymal stem cells derived from bone marrow after cerebral ischemia.Brain Res. 2010;1334:84-92.

[12] Solaroglu I, Cahill J, Tsubokawa T, et al. Granulocyte colony-stimulating factor protects the brain against experimental stroke via inhibition of apoptosis and inflammation. Neurol Res. 2009;31(2):167-172.

[13] 郭振宇,郑芹,雷俊霞,等.不同品系小鼠骨髓问质干细胞扩增能力及细胞表型差异的比较[J].中国组织工程研究与临床康复,2008, 47(12)-9257-9260.

[14] Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9(1):11-15.

[15] Charbord P, Livne E, Gross G, et al. Human bone marrow mesenchymal stem cells: a systematic reappraisal via the genostem experience. Stem Cell Rev. 2011;7(1):32-42.

[16] Hicks AU, Lappalainen RS, Narkilahti S, et al. Transplantation of human embryonic stem cell-derived neural precursor cells and enriched environment after cortical stroke in rats: cell survival and functional recovery. Eur J Neurosci. 2009;29(3): 562-574.

[17] Li Y, Chopp M. Marrow stromal cell transplantation in stroke and traumatic brain injury. Neurosci Lett. 2009;456(3): 120-123.

[18] 吴晓牧,屈新辉,张洪连,等.颈动脉移植骨髓间充质干细胞治疗脑梗死大鼠[J].中华神经科杂志,2011,44(7):487-492.

[19] Buffo A, Rolando C, Ceruti S. Astrocytes in the damaged brain: molecular and cellular insights into their reactive response and healing potential. Biochem Pharmacol. 2010;79(2):77-89.

[20] Zhang D, Fan GC, Zhou X, et al. Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. J Mol Cell Cardiol. 2008;44(2):281-292.

[21] Higuchi T, Anton M, Saraste A, et al. Reporter gene PET for monitoring survival of transplanted endothelial progenitor cells in the rat heart after pretreatment with VEGF and atorvastatin. J Nucl Med. 2009;50(11):1881-1886.

[22] Ben Azouna N, Jenhani F, Regaya Z, et al. Phenotypical and functional characteristics of mesenchymal stem cells from bone marrow: comparison of culture using different media supplemented with human platelet lysate or fetal bovine serum. Stem Cell Res Ther. 2012;3(1):6.

[23] Knoop K, Schwenk N, Dolp P, et al. Stromal targeting of sodium iodide symporter using mesenchymal stem cells allows enhanced imaging and therapy of hepatocellular carcinoma. Hum Gene Ther. 2013;24(3):306-316.

[24] Liu Z, Li Y, Zhang ZG, et al. Bone marrow stromal cells enhance inter- and intracortical axonal connections after ischemic stroke in adult rats. J Cereb Blood Flow Metab. 2010;30(7):1288-1295.

[25] Yu YL, Chou RH, Shyu WC, et al. Smurf2-mediated degradation of EZH2 enhances neuron differentiation and improves functional recovery after ischaemic stroke. EMBO Mol Med. 2013;5(4):531-547.

[26] Raghavan A, Shah ZA. Repair and regeneration properties of Ginkgo biloba after ischemic brain injury. Neural Regen Res. 2014;9 (11): 1104-1107.

[27] Xia W, Li H, Wang Z, et al. Human platelet lysate supports ex vivo expansion and enhances osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Cell Biol Int. 2011;35(6):639-643.

[28] Wang JW,Chen W,Wang YL.A ginkgo biloba extract promotes proliferation of endogenous neural stem cells in vascular dementia rats.Neural Regen Res. 2013;8(18): 1655-1662

[29] 王雪松, 阮旭中,刘买利. 银杏叶提取物(GBE)对大鼠局灶性脑缺血后细胞间黏附分子-1及其mRNA表达的影响[J].中国现代应用药学,2008,20(6):441-444.

[30] 张勇,程敬亮,王娟,等.SHU555A标记大鼠骨髓间充质干细胞的磁敏感加权成像[J].实用放射学杂志,2010,26(5):736-739.

[31] Wang H, Cao F, De A, et al. Trafficking mesenchymal stem cell engraftment and differentiation in tumor-bearing mice by bioluminescence imaging. Stem Cells. 2009;27(7):1548-1558.