Mechanism and Progress of MSC Derived Extracellular Vesicles in the Treatment of Ischemic Stroke
-
摘要: 缺血性脑卒中是由于脑动脉血流中断从而导致细胞缺氧和氧化应激,同时激活炎症反应,造成组织细胞损伤,增加细胞凋亡和血液再灌注的风险。间充质干细胞可以通过诱导血管生成来改善缺血性脑卒中程度,同时间充质干细胞还具有抗凋亡,抗炎等诸多功能,被应用于卒中治疗。临床前期研究证实,间充质源外泌体通过靶向传递到受体细胞起到诱导血管生成,抗凋亡和抗炎的效果,也避免了间充质干细胞在治疗过程中存在的不足,进而用于卒中治疗。现系统地对间充质干细胞源外泌体在脑卒中中的作用机理进行总结,为缺血性脑血管病的临床治疗提供一种新的可能性,以期获得更好的治疗效果。Abstract: Cerebral ischemic stoke is a disease in which oxidative stress, activation of inflammatory storms, interference, induction of apoptosis, and blood reperfusion aggravate the tissue and cell damage due to ischemia and hypoxia. Mesenchymal stem cells(MSCs) induce the angiogenesis and can be used to treat the ischemia-reperfusion injury, anti-apoptosis and anti-inflammatory. Preclinical studies have confirmed that targeted delivery of mesenchymal-derived exosomes to recipient cells exerts the effects of inducing angiogenesis, anti-apoptosis, and anti-inflammatory, while avoiding the shortcomings of mesenchymal stem cell therapy. The purpose of this study is to summarize the mechanism of exosomes derived from mesenchymal stem cells in the treatment of stroke so as to provide new opportunities for treating ischemic cerebrovascular disease clinically.
-
Key words:
- Mesenchymal stem cells /
- Exosomes /
- Stroke
-
[1] Donald G Phinney,Mark F Pittenger. Concise review:MSC-derived exosomes for cell-free therapy[J]. Stem Cells (Dayton,Ohio),2017,35(4):851-858. doi: 10.1002/stem.2575 [2] Zhao Yangmin,Gan Yunxiao,Xu Gewei,et al. MSC-derived exosomes attenuate acute brain injury and inhibit microglial inflammation by reversing cyslt2r-erk1/2mediated microglia M1 polarization[J]. Neurochemical Research,2020,45(5):1180-1190. doi: 10.1007/s11064-020-02998-0 [3] Jennifer Phan, Priyadarsini Kumar, Dake Hao, et al, Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell-free therapy [J]. J Extracell Vesicles, 2018, 7(1): 1522236. [4] Farzamfar S,Hasanpour A,Nazeri N,et al. Extracellular micro/nanovesicles rescue kidney from ischemia-reperfusion injury[J]. Journal of Cellular Physiology,2019,234(8):12290-12300. doi: 10.1002/jcp.27998 [5] Danica Petrovic-Djergovic,Sascha N Goonewardena,David J Pinsky. Inflammatory disequilibrium in stroke[J]. Circulation Research,2016,119(1):142-58. doi: 10.1161/CIRCRESAHA.116.308022 [6] 汪亮. 葛根素对大鼠局灶性脑缺血再灌注损伤后TLR4/NF-κB信号通路的影响[D]. 宁波: 宁波大学博士学位论文, 2012. [7] 聂金,戴爱国,胡瑞成. 缺氧诱导因子脯氨酸羟化酶的调控与缺血缺氧性疾病[J]. 临床与病理杂志,2007,27(1):53-56. doi: 10.3969/j.issn.1673-2588.2007.01.013 [8] Yu fang S,Yu W,Qing L,et al. Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases[J]. Nature Reviews Nephrology,2018,14(8):493-507. doi: 10.1038/s41581-018-0023-5 [9] Tavasolian Fataneh,Moghaddam Abbas Shapouri,Rohani Fattah,et al. Exosomes:Effectual players in rheumatoid arthritis[J]. Autoimmunity Reviews,2020,19(6):102511-102518. [10] Zou X,Zhang G,Cheng Z,et al. Microvesicles derived from human Wharton's Jelly mesenchymal stromal cells ameliorate renal ischemia-reperfusion injury in rats by suppressing CX3CL1[J]. Stem Cell Research & Therapy,2014,5(2):1-13. doi: 10.1186/scrt428 [11] Zou Xiangyu,Zhang Guangyuan,Cheng Zhongliang,et al. Microvesicles derived from human Wharton's Jelly mesenchymal stromal cells ameliorate renal ischemia-reperfusion injury in rats by suppressing CX3CL1[J]. Stem Cell Research & Therapy,2014,5(2):40-52. [12] Zhao J,Li X,Hu J,et al. Mesenchymal stromal cell-derived exosomes attenuate myocardial ischemia-reperfusion injury through miR-182-regulated macrophage polarization[J]. Cardiovascular Research,2019,115(7):1205-1216. doi: 10.1093/cvr/cvz040 [13] Liu J,Chen T,Lei P,et al. Exosomes released by bone marrow mesenchymal stem cells attenuate lung injury induced by intestinal ischemia reperfusion via the tlr4-nf-κbpathway[J]. International Journal of Medical[J]. Sciences,2019,16(9):1238-1244. doi: 10.7150/ijms.35369 [14] Wilson C M,Naves T,Vincent F,et al. Sortilin mediates the release and transfer of exosomes in concert with two tyrosine kinase receptors.[J]. Journal of Cell Science,2014,127(18):3983-3997. [15] Sinh N D,Endo K,Miyazawa K,et al. Ets1 and ESE1 reciprocally regulate expression of ZEB1/ZEB2,dependent on ERK1/2 activity,in breast cancer cells[J]. Cancer Science,2017,108(5):952-960. doi: 10.1111/cas.13214 [16] Long G , Wang F , Duan Q , et al, Human circulating microRNA-1 and microRNA-126 as potential novel indicators for acute myocardial infarction[J]. International Journal of Biological Ences, 2012, 8(6): 811-818. [17] Chen Zhe,Wang Hanqi,Xia Yang,et al. Therapeutic potential of mesenchymal cell–derived miRNA-150-5p–expressing exosomes in rheumatoid arthritis mediated by the modulation of MMP14 and VEGF[J]. J Immunol,2018,201(8):2472-2482. doi: 10.4049/jimmunol.1800304 [18] 詹小舒,罗惠娜,罗冬章,等. 犬脐带间充质干细胞来源外泌体对血管内皮细胞增殖、迁移和凋亡的调控作用[J]. 中国组织工程研究,2019,23(29):4637-4643. doi: 10.3969/j.issn.2095-4344.1808 [19] 赵金璇. 间充质干细胞外泌体对心肌缺血再灌注后巨噬细胞极化的影响及作用机制研究[D]. 南京: 南京大学博士学位论文, 2019. [20] 郝海珍,郭铁,余丹. 脂肪间充质干细胞来源外泌体对脑缺血再灌注大鼠神经元凋亡及炎症因子影响[J]. 第三军医大学学报,2019,41(17):1656-1665. doi: 10.16016/j.1000-5404.201904034 [21] Wang Z,Xie H,Zhou L,et al. CCL2/CCR2 axis is associated with postoperative survival and recurrence of patients with non-metastatic clear-cell renal cell carcinoma[J]. Oncotarget,2016,7(32):51525-51534. doi: 10.18632/oncotarget.10492 [22] 张娟,史晋叔,李剑. 间充质干细胞源性外泌体—未来生物疗法的理想载体[J]. 中国实验血液学杂志,2015,23(4):1179-1183. doi: 10.1016/j.stem.2009.05.003 [23] Lee R H,Pulin A A,Seo M J,et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6[J]. Cell Stem Cell,2009,5(1):54-63. [24] Merino-González C,Zuñiga F A,Escudero C,et al. Mesenchymal stem cell-derived extracellular vesicles promote angiogenesis: Potencial clinical application[J]. Frontiers in Physiology,2016,7(24):24-32. [25] Ravichandran R,Itabashi Y,Liu W,et al. A decline in club cell secretory proteins in lung transplantation is associated with release of natural killer cells exosomes leading to chronic rejection.[J]. The Journal of Heart and Lung Transplantation:The Official Publication of the International Society for Heart Transplantation,2021,40(12):1517-1528. doi: 10.1016/j.healun.2021.08.016 [26] Riazifar M,Mohammadi M R,Pone E J,et al. Stem cell-derived exosomesas nanotherapeutics for autoimmune and neurodegenerative disorders[J]. Acs Nano,2019,13(6):6670-6688. doi: 10.1021/acsnano.9b01004 [27] Zhuang X,Xiang X,Grizzle W,et al. Treatment of brain inflammatory diseases by delivering exosomeencapsulated anti-inflammatory drugs from the nasal region to the brain[J]. Mol Ther,2011,19(10):1769-1779. [28] Jiang X C, Gao J Q. Exosomes as novel bio-carriers for gene and drug delivery[J]. Int J Pharm,2017,521(1-2):167-175. [29] Xin H,Li Y,Buller B,et al. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth[J]. Stem Cells,2012,30(7):1556-1564. [30] Xu W,Yang Z,Lu N. From pathogenesis to clinical application: Insights into exosomes as transfer vectors in cancer[J]. Journal of Experimental & Clinical Cancer Research Cr,2016,35(1):156-167. [31] Wang J,Li W,Lu Z,et al. The use of RGD-engineered exosomes for enhanced targeting ability and synergistic therapy toward angiogenesis[J]. Nanoscale,2017,9(40):15598-15605. doi: 10.1039/C7NR04425A
点击查看大图
计量
- 文章访问数: 1790
- HTML全文浏览量: 774
- PDF下载量: 27
- 被引次数: 0