干细胞治疗阿尔茨海默病的研究现状及发展趋势
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摘要
背景:阿尔茨海默病是一种脑退行性疾病,目前药物对其治疗无明显效果,干细胞移植为其提供了一个新的治疗手段。目的:揭示干细胞治疗阿尔茨海默病的主题、演进路径和研究进展,以期对阿尔茨海默病的研究和临床治疗提供参考。方法:检索中国知网、中国生物医学文献数据库、ISI Web of Knowledge数据库和Embace数据库,以"Alzheimer’s disease""stem cell""阿尔茨海默病""干细胞"+"阿尔茨海默病"为关键词检索相关文献,运用Cite Space软件对干细胞治疗阿尔茨海默病进行可视化知识图谱分析和文献梳理。结果与结论:干细胞治疗阿尔茨海默病研究的演进路径与干细胞移植研究密切相关。该研究主线单一且突出,围绕"阿尔茨海默病——干细胞、神经干细胞——移植——骨髓间充质干细胞、间充质干细胞、人脐带间充质干细胞、β-淀粉样蛋白——组织工程"等关键词和由其构成的核心领域而展开和实施的。人类干细胞临床试验也已处于初期阶段,应重视使用干细胞的安全性、有效性及伦理问题,将干细胞分化调控作为研究重点,尽早实现个体化的干细胞治疗,为阿尔茨海默病患者带来曙光。
BACKGROUND: Alzheimer's disease is a degenerative brain disease, and there are no known drugs for curing Alzheimer's disease. Stem cell transplantation provides a new therapeutic method for Alzheimer's disease. OBJECTIVE: To reveal the theme, evolutionary path and research progress of stem cell therapy for Alzheimer's disease, in a bid to provide reference for the research and clinical treatment of Alzheimer's disease. METHODS: A computer search of CNKI, CBM, ISI Web of knowledge, and Embace was performed with the keywords of "Alzheimer's disease" and "stem cells" + "Alzheimer's disease," in Chinese and English, respectively. We conducted a visualized knowledge mapping and literature review of stem cell therapy for Alzheimer's disease using CiteSpace software.RESULTS AND CONCLUSION: The evolutionary path of research on stem cell therapy for Alzheimer's disease is closely related to stem cell transplantation research. The main line of this research is single and prominent, which is developed and implemented based on the keywords of "Alzheimer's disease-stem cells, neural stem cells-transplantation-bone marrow mesenchymal stem cells, mesenchymal stem cells, human umbilical cord mesenchymal stem cells, beta-amyloid-tissue engineering," and the core domains composed by these keywords. Human stem cell clinical trials are ongoing in the early stage. The safety, efficacy and ethical issues of stem cells should be emphasized. The regulation of stem cell differentiation should become an issue of concern, and individualized stem cell treatment should be implemented as soon as possible.
BACKGROUND: Alzheimer's disease is a degenerative brain disease, and there are no known drugs for curing Alzheimer's disease. Stem cell transplantation provides a new therapeutic method for Alzheimer's disease. OBJECTIVE: To reveal the theme, evolutionary path and research progress of stem cell therapy for Alzheimer's disease, in a bid to provide reference for the research and clinical treatment of Alzheimer's disease. METHODS: A computer search of CNKI, CBM, ISI Web of knowledge, and Embace was performed with the keywords of "Alzheimer's disease" and "stem cells" + "Alzheimer's disease," in Chinese and English, respectively. We conducted a visualized knowledge mapping and literature review of stem cell therapy for Alzheimer's disease using CiteSpace software.RESULTS AND CONCLUSION: The evolutionary path of research on stem cell therapy for Alzheimer's disease is closely related to stem cell transplantation research. The main line of this research is single and prominent, which is developed and implemented based on the keywords of "Alzheimer's disease-stem cells, neural stem cells-transplantation-bone marrow mesenchymal stem cells, mesenchymal stem cells, human umbilical cord mesenchymal stem cells, beta-amyloid-tissue engineering," and the core domains composed by these keywords. Human stem cell clinical trials are ongoing in the early stage. The safety, efficacy and ethical issues of stem cells should be emphasized. The regulation of stem cell differentiation should become an issue of concern, and individualized stem cell treatment should be implemented as soon as possible.
引文
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[2]李坤埔,王勇.干细胞治疗阿尔茨海默病的研究进展[J].四川解剖学杂志,2016,24(4):43-47.
[3]刘晓峰,吴迪,吴岩.干细胞治疗阿尔茨海默病的现状及未来[J].中国组织工程研究,2013,17(40):7132-7137.
[4]Aisen PS,Cummings J,Jack CR Jr,et al.On the path to 2025:understanding the Alzheimer's disease continuum.Alzheimers Res Ther.2017;9(1):60.
[5]侯剑华,胡志刚.CiteSpace软件应用研究的回顾与展望[J].现代情报,2013,33(4):99-103.
[6]Xiao F,Li C,Sun J,et al.Knowledge Domain and Emerging Trends in Organic Photovoltaic Technology:A Scientometric Review Based on CiteSpace Analysis.Front Chem.2017;5:67.
[7]Liang C,Luo A,Zhong Z.Knowledge mapping of medication literacy study:A visualized analysis using CiteSpace.SAGE Open Med.2018;6:2050312118800199.
[8]张新宇,付学锋.神经干细胞移植治疗阿尔茨海默病研究现状[J].医学综述,2011,17(20):3067-3070.
[9]于程程,张斌,陈虎.干细胞移植治疗阿尔茨海默病的研究现状及展望[J].中国组织工程研究,2012,16(23):4301-4305.
[10]孔迪,殷香宇,申龙健,等.阿尔茨海默病的细胞及基因疗法研究现状[J].医学综述,2015,21(18):3299-3301.
[11]朱琼,徐亚丽,刘政.神经干细胞治疗阿尔茨海默病的研究进展[J].重庆医学,2016,45(30):4286-4288.
[12]Kwak KA,Lee SP,Yang JY,et al.Current Perspectives regarding Stem Cell-Based Therapy for Alzheimer's Disease.Stem Cells Int.2018;2018:6392986.
[13]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,2011,2(31):218-211.
[14]Bali P,Lahiri DK,Banik A,et al.Potential for Stem Cells Therapy in Alzheimer's Disease:Do Neurotrophic Factors Play Critical Role.Curr Alzheimer Res.2017;14(2):208-220.
[15]Duncan T,Valenzuela M.Alzheimer's disease,dementia,and stem cell therapy.Stem Cell Res Ther.2017;8(1):111.
[16]曹云鹏.干细胞治疗阿尔茨海默病的研究进展[J].中国内科实用杂志,2007,27(10):748-750.
[17]Tincer G,Mashkaryan V,Bhattarai P,et al.Neural stem/progenitor cells in Alzheimer's disease.Yale J Biol Med.2016;89(1):23-35.
[18]Qu T,Brannen CL,Kim HM,et al.Human neural stem cells improve cognitive function of aged brain.Neuroreport.2001;12(6):1127-1132.
[19]张宇,杨萌萌,康红军.间充质干细胞治疗阿尔茨海默病的研究进展[J].解放军医学院学报,2017,38(6):565-567,574.
[20]袁佳欣,管丽娜,王梅慧,等.人类间充质干细胞治疗阿尔茨海默病相关调控的研究进展[J].中国实用神经病学杂志,2018,21(13):1494-1498.
[21]Chen CM.CiteSpace II:Detecting and visualizing emerging trends and transient patterns in scientific literature.Journal of the American Society for Information Science and Technology.2006;57(3):359-377.
[22]陈悦,陈超美,刘则渊,等.CiteSpace知识图谱的方法论功能[J].科学研究,2015,33(2):242-253.
[23]Chen J,Su Y,Si H,et al.Managerial Areas of Construction and Demolition Waste:A Scientometric Review.Int J Environ Res Public Health.2018;15(11):E2350.
[24]Zhang SC,Wernig M,Duncan ID,et al.In vitro differentiation of transplantable neural precursors from human embryonic stem cells.Nat Biotechnol.2001;19(12):1129-1133.
[25]Gray JA,Grigoryan G,Virley D,et al.Conditionally immortalized,multipotential and multifunctional neural stem cell lines as an approach to clinical transplantation.Cell Transplant.2000;9(2):153-168.
[26]Tate BA,Werzanski D,Marciniak A,et al.Migration of neural stem cells to Alzheimer-like lesions in an animal model of AD.Soc Neurosci Abstr.2000;26(2):496-497.
[27]Kim HM,Qu T,Kriho V,et al.Reelin function in neural stem cell biology.Proc Natl Acad Sci U S A.2002;99(6):4020-4025.
[28]Kim SU,Lee HJ,Kim YB.Neural stem cell-based treatment for neurodegenerative diseases.Europathology.2013;33(5):491-504.
[29]徐海伟,黎海蒂.神经前体细胞的迁移机制及其应用研究进展[J].生理科学进展,2004,35(1):42-45.
[30]Wu P,Tarasenko YI,Gu Y,et al.Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat.Nat Neurosci.2002;5(12):1271-1278.
[31]Broersen K,Jonckheere W,Rozenski J,et al.A standardized and biocompatible preparation of aggregate-free amyloid beta peptide for biophysical and biological studies of Alzheimer's disease.Protein Eng Des Sel.2011;24(9):743-750.
[32]Risacher SL,Anderson WH,Charil A,et al.Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline.Neurology.2017;89(21):2176-2186.
[33]Hampel H,Wilcock G,Andrieu S,et al.Biomarkers for Alzheimer's disease therapeutic trials.Prog Neurobiol.2011;95(4):579-593.
[34]Van Dam D,Vermeiren Y,Dekker AD,et al.Neuropsychiatric Disturbances in Alzheimer's Disease:What Have We Learned from Neuropathological Studies.Curr Alzheimer Res.2016;13(10):1145-1164.
[35]任汝静,陈生弟.阿尔茨海默病的治疗现状和展望[J].中国现代神经疾病杂志,2005,5(3):147-151.
[36]林盛.阿尔茨海默病68例药物治疗效果及发病机制探讨[J].当代医学,2012,18(33):10-11.
[37]单媛莉,常富业.阿尔茨海默病药物治疗的概述与展望[J].现代中西医结合杂志,2013,22(6):670-673.
[38]Cummings J,Aisen PS,DuBois B,et al.Drug development in Alzheimer's disease:the path to 2025.Alzheimers Res Ther.2016;8:39.
[39]Bachurin SO,Bovina EV,Ustyugov AA.Drugs in Clinical Trials for Alzheimer's Disease:The Major Trends.Med Res Rev.2017;37(5):1186-1225.
[40]Lemere CA.Developing novel immunogens for a safe and effective Alzheimer's disease vaccine.Prog Brain Res.2009;175:83-93.
[41]Pasquier F,Sadowsky C,Holstein A,et al.Two Phase 2 Multiple Ascending-Dose Studies of Vanutide Cridificar(ACC-001)and QS-21Adjuvant in Mild-to-Moderate Alzheimer's Disease.J Alzheimers Dis.2016;51(4):1131-1143.
[42]Davtyan H,Bacon A,Petrushina I,et al.Immunogenicity of DNA-and recombinant protein-based Alzheimer disease epitope vaccines.Hum Vaccin Immunother.2014;10(5):1248-1255.
[43]Thomson JA,Itskovitz-Eldor J,Shapiro SS,et al.Embryonic stem cell lines derived from human blastocysts.Science.1998;282(5391):1145-1147.
[44]张喻,肇玉明,王晓良,等.干细胞治疗阿尔茨海默病的研究进展及挑战[J].中国药理学通报,2015,31(7):889-894.
[45]Park D,Yang YH,Bae DK,et al.Improvement of cognitive function and physical activity of aging mice by human neural stem cells over-expressing choline acetyltransferase.Neurobiol Aging.2013;34(11):2639-2646.
[46]Sullivan R,Duncan K,Dailey T,et al.A possible new focus for stroke treatment-migrating stem cells.Expert Opin Biol Ther.2015;15(7):949-958.
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