内皮祖细胞治疗缺血性脑血管病的研究进展

摘要/Abstract

摘要：

内皮祖细胞（endothelial progenitor cell，EPC）可促进缺血损伤后脑组织血管新生及神经发生。近年来，移植外源性EPC、动员内源性EPC等治疗方法在缺血性脑血管病的实验研究中开辟了新的途径，并证实EPC在外周血中的水平对缺血性脑血管病的严重性及预后具有预测价值。本文对EPC治疗缺血性脑血管病的作用机制，治疗策略，在临床应用中尚存在的问题，以及最新研究进展做一综述。

文章导读： 本文对内皮祖细胞治疗缺血性脑血管病的作用机制，治疗策略，以及在临床应用中尚存在的问题展开阐述。

关键词: 内皮祖细胞; 缺血性脑血管病; 治疗策略

Abstract:

Endothelial progenitor cell (EPC) can promote the angiogenesis and the neurogenesis in the cerebral ischemic injury. In recent years, the therapeutic strategy such as transplanting EPC or mobilizing EPC opens a new avenue in the experimental research, and it has demonstrated that the level of EPC in the peripheral blood has a predictive value in the severity and prognosis of ischemic cerebrovascular disease. In this article, we make a review of the mechanism of EPC in the treatment, the therapeutic strategy, the existing problems in the clinical application, as well as the advances in the latest research.

Key words: Endothelial progenitor cell; Ischemic cerebrovascular disease; Therapeutic strateg

李雨浓，朱雨岚. 内皮祖细胞治疗缺血性脑血管病的研究进展[J]. 中国卒中杂志, 2015, 10(06): 513-518.

LI Yu-Nong, ZHU Yu-Lan. Advances in the Treatment of Endothelial Progenitor Cell in Ischemic Cerebrovascular Disease[J]. Chinese Journal of Stroke, 2015, 10(06): 513-518.

参考文献

1 Molina CA. Reperfusion therapies for acute ischemic stroke current pharmacological and mechanical approaches[J]. Stroke, 2011, 42:S16-S19.

2 Adeoye O, Hornung R, Khatri P, et al. Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States:A doubling of treatment rates over the course of 5 years[J]. Stroke, 2011, 42:1952-1955.

3 Lo EH. A new penumbra:transitioning from injury into repair after stroke[J]. Nat Med, 2008, 14:497-500.

4 Rehman J, Li J, Orschell CM, et al. Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors[J]. Circulation, 2003, 107:1164-1169.

5 Urbich C, Aicher A, Heeschen C, et al. Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells[J]. J Mol Cell Cardiol, 2005, 39:733-742.

6 Lampugnani MG, Resnati M, Raiteri M, et al. A novel endothelial-specific membrane protein is a marker of cell-cell contacts[J]. J Cell Biol, 1992, 118:1511-1522.

7 Murota SI, Onodera M, Morita I. Regulation of angiogenesis by controlling VEGF receptor[J]. Ann N Y Acad Sci, 2000, 902:208-212.

8 Rosell A, Morancho A, Navarro-Sobrino M, et al. Factors secreted by endothelial progenitor cells enhance neurorepair responses after cerebral ischemia in mice[J]. PLoS One, 2013, 8:e73244.

9 杜公文, 杜怡斌, 张辉, 等. 共培养下内皮祖细胞对神经干细胞增殖及分化的影响[J]. 安徽医科大学学报, 2013, 48:1445-1449.

10 Thored P, Wood J, Arvidsson A, et al. Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke[J]. Stroke, 2007, 38:3032-3039.

11 齐志国, 梁红梅, 朱晓峰, 等. EPCs与NSCs共移植对 MCAO模型大鼠神经功能缺损恢复影响[J]. 激光杂志, 2010, 31:86-87.

12 Taguchi A, Zhu P, Cao F, et al. Reduced ischemic brain injury by partial rejuvenation of bone marrow cells in aged rats[J]. J Cereb Blood Flow Metab, 2010, 31:855-867.

13 Moubarik C, Guillet B, Youssef B, et al. Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke[J]. Stem Cell Rev, 2011, 7:208-220.

14 Chen ZZ, Jiang XD, Zhang LL, et al. Beneficial effect of autologous transplantation of bone marrow stromal cells and endothelial progenitor cells on cerebral ischemia in rabbits[J]. Neurosci Lett, 2008, 445:36-41.

15 Fan Y, Shen F, Frenzel T, et al. Endothelial progenitor cell transplantation improves long-term stroke outcome in mice[J]. Ann Neurol, 2010, 67:488-497.

16 Churdchomjan W, Kheolamai P, Manochantr S, et al. Comparison of endothelial progenitor cell function in type 2 diabetes with good and poor glycemic control[J]. BMC Endocr Disord, 2010, 10:5.

17 Silver AE, Beske SD, Christou DD, et al. Overweight and obese humans demonstrate increased vascular endothelial NAD (P) H oxidase-p47phox expression and evidence of endothelial oxidative stress[J]. Circulation, 2007, 115:627-637.

18 Tu S, Shao A, Ren L, et al. Angiogenesis effect of Astragalus polysaccharide combined with endothelial progenitor cells therapy in diabetic male rat following experimental hind limb ischemia[J]. Chin Med J(Engl), 2014, 127:2121-2128.

19 Wassmann S, Werner N, Czech T, et al. Improvement of endothelial function by systemic transfusion of vascular progenitor cells[J]. Circ Res, 2006, 99:e74-e83.

20 Sen S, Merchan J, Dean J, et al. Autologous transplantation of endothelial progenitor cells genetically modified by adeno-associated viral vector delivering insulin-like growth factor-1 gene after myocardial infarction[J]. Hum Gene Ther, 2010, 21:1327-1334.

21 Yu JX, Huang XF, Lv WM, et al. Combination of stromal-derived factor-1α and vascular endothelial growth factor gene-modified endothelial progenitor cells is more effective for ischemic neovascularization[J]. J Vasc Surg, 2009, 50:608-616.

22 薛奋龙, 陈庆良, 简锴陶, 等. 缺氧预处理对骨髓来源内皮祖细胞生物学功能的影响[J]. 天津医药, 2014, 42:231-234.

23 Akita T, Murohara T, Ikeda H, et al. Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization[J]. Lab Invest, 2003, 83:65-73.

24 Qin W, Li Z, Luo S, et al. Exogenous fractalkine enhances proliferation of endothelial cells, promotes migration of endothelial progenitor cells and improves neurological deficits in a rat model of ischemic stroke[J]. Neurosci Lett, 2014, 569:80-84.

25 赵瑛, 陈斯佳, 于文娟, 等. 电针刺激对脑缺血大鼠内源性EPCs及相关血清细胞因子的影像[J]. 生物医学工程学杂志, 2010, 27:1322-1326.

26 Wang W, Lang JK, Suzuki G, et al. Statins enhance clonal growth of late outgrowth endothelial progenitors and increase myocardial capillary density in the chronically ischemic heart[J]. PLoS One, 2011, 6:e24868.

27 Honda A, Matsuura K, Fukushima N, et al. Telmisartan induces proliferation of human endothelial progenitor cells via PPARgamma-dependent PI3K/Akt pathway[J]. Atherosclerosis, 2009, 205:376-384.

28 Müller P, Kazakov A, Jagoda P, et al. ACE inhibition promotes upregulation of endothelial progenitor cells and neoangiogenesis in cardiac pressure overload[J]. Cardiovasc Res, 2009, 83:106-114.

29 Zhang Y, Ingram DA, Murphy MP, et al. Release of proinflammatory mediators and expression of proinflammatory adhesion molecules by endothelial progenitor cells[J]. Am J Physiol Heart Circ Physiol, 2009, 296:H1675-H1682.

30 Yang Z, Di Santo S, Kalka C. Current developments in the use of stem cell for therapeutic neovascularisation:is the future therapy "cell-free"[J]. Swiss Med Wkly, 2010, 140:w13130.

31 Zhou WJ, Zhu DL, Yang GY, et al. Circulating endothelial progenitor cells in Chinese patients with acute stroke[J]. Hypertens Res, 2009, 32:306-310.

32 Sobrino T, Hurtado O, Moro MÁ, et al. The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome[J]. Stroke, 2007, 38:2759-2764.

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

34 Seminatore C, Polentes J, Ellman D, et al. The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors[J]. Stroke, 2010, 41:153-159.

35 Chen J, Chen S, Chen Y, et al. Circulating endothelial progenitor cells and cellular membrane microparticles in db/db diabetic mouse:possible implications in cerebral ischemic damage[J]. Am J Physiol Endocr Metab, 2011, 301:E62-E71.

36 Hu Y, Davison F, Zhang Z, et al. Endothelial replacement and angiogenesis in arteriosclerotic lesions of allografts are contributed by circulating progenitor cells[J]. Circulation, 2003, 108:3122-3127.

[1]	杨红娜, 冀瑞俊, 于凯, 何艳, 徐丽华, 王拥军. 缺血性脑血管病二级预防药物依从性及其影响因素研究 [J]. 中国卒中杂志, 2022, 17(11): 1227-1232.
[2]	张彤, 王安心, 安媛, 张亚清, 刘艳芳, 赵性泉. 脑动脉前循环串联病变临床治疗效果meta分析[J]. 中国卒中杂志, 2022, 17(05): 503-509.
[3]	幸章力，薛蕴菁. 区域性动脉自旋标记在缺血性脑血管病中的应用进展[J]. 中国卒中杂志, 2021, 16(01): 87-91.
[4]	陈玮琪, 张国军, 潘岳松, 林金嬉, 梁宪红, 李上智, 王伊龙, 荆京, 赵性泉, 刘丽萍, 王拥军. 胰岛素抵抗与非致残性缺血性脑血管病患者卒中复发之间的关系[J]. 中国卒中杂志, 2019, 14(10): 1004-1010.
[5]	王光耀, 荆京, 孟霞, 刘丽萍, 赵性泉, 王拥军, 王伊龙. 缺血性脑血管病梗死模式的分类及病因、发病机制研究进展[J]. 中国卒中杂志, 2019, 14(09): 950-954.
[6]	孟霞，张星，吕微，张心邈，荆京，谷鸿秋. 缺血性脑血管病二级预防药物依从性与卒中复发的关系研究[J]. 中国卒中杂志, 2019, 14(07): 653-659.
[7]	刘丽萍，陈玮琪，段婉莹，等，中国卒中学会中国脑血管病临床管理指南撰写委员会（*第一作者）. 中国脑血管病临床管理指南（节选版）—— 缺血性脑血管病临床管理[J]. 中国卒中杂志, 2019, 14(07): 709-726.
[8]	张长青，赵性泉，王春雪，王伊龙，王拥军. 以问题为基础教学法在急性缺血性脑血管病临床教学中的应用研究[J]. 中国卒中杂志, 2019, 14(02): 188-190.
[9]	周知微，马萌萌，何俐. 高危非致残性缺血性脑血管事件与认知障碍[J]. 中国卒中杂志, 2017, 12(12): 1123-1126.
[10]	彭炜，张兆耘，殷秀萍，王玉梅. 沙漠化地区缺血性脱髓鞘性脑白质病变危险因素研究[J]. 中国卒中杂志, 2017, 12(11): 991-994.
[11]	邵晓军，杨静，王遐，张晨. 单纯颅内动脉狭窄性缺血性脑血管病预后评估[J]. 中国卒中杂志, 2017, 12(11): 1005-1009.
[12]	李姝雅，王伊龙，王春雪，刘改芬，王拥军. 姜黄素对大脑中动脉缺血模型大鼠的神经保护作用及机制研究[J]. 中国卒中杂志, 2016, 11(12): 1035-1039.
[13]	赵韧，靳航，郭珍妮，吕珊，杨弋. 脑血流调节在脑血管再通治疗中的应用[J]. 中国卒中杂志, 2016, 11(04): 301-305.
[14]	饶子龙，郑华光，王菲，王安心，刘丽萍，董可辉，曲辉，龚浠平，张倩，赵性泉，陆菁菁，鞠奕，方瑞乐，王文娟，杨中华，温淼，魏娜，濮月华，王伊龙，曹亦宾. 血栓弹力图凝血酶原通道检测指标在评价急性缺血性脑血管病患者高血小板反应性以及预测复发缺血事件中的价值[J]. 中国卒中杂志, 2016, 11(03): 207-214.
[15]	王拥军. 跨界思维[J]. 中国卒中杂志, 2016, 11(02): 93-94.