PDF(Pubmed)
Abstract：
Neural stem cell (NSC) transplantation is an emerging and promising approach to combat neurodegenerative diseases. While NSCs can differentiate into neural cell types, many therapeutic effects are mediated by paracrine, \"drug-like\" mechanisms. Neurodegenerative diseases are predominantly a burden of the elderly who commonly suffer from comorbidities and thus are subject to pharmacotherapies. There is substantial knowledge about drug-drug interactions but almost nothing is known about a potential impact of pharmacotherapy on NSCs. Such knowledge is decisive for designing tailored treatment programs for individual patients. Previous studies revealed preliminary evidence that the anti-depressants fluoxetine and imipramine may affect NSC viability and proliferation. Here, we derive a hypothesis on how commonly applied drugs, statins and antihypertensives, may affect NSC viability, proliferation, and differentiation. We conducted a systematic review and meta-analysis looking at potential effects of commonly prescribed antihypertensive and antihyperlipidemic medication on NSC function. PubMed and Web of Science databases were searched on according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Publications were assessed against a priori established selection criteria for relevancy. A meta-analysis was then performed on data extracted from publications eligible for full text review to estimate drug effects on NSC functions. Our systematic review identified 1,017 potential studies, 55 of which were eligible for full text review. Out of those, 21 were included in the qualitative synthesis. The meta-analysis was performed on 13 publications; the remainder were excluded as they met exclusion criteria or lacked sufficient data to perform a meta-analysis. The meta-analysis revealed that alpha-2 adrenoceptor agonists, an anti-hypertensive drug class [p < 0.05, 95% confidence intervals (CI) = -1.54; -0.35], and various statins [p < 0.05, 95% CI = -3.17; -0.0694] had an inhibiting effect on NSC proliferation. Moreover, we present preliminary evidence that L-type calcium channel blockers and statins, particularly lovastatin, may reduce NSC viability. Although the data available in the literature is limited, there are clear indications for an impact of commonly applied drugs, in particular statins, on NSC function. Considering the modes of action of the respective drugs, we reveal plausible mechanisms by which this impact may be mediated, creating a testable hypothesis, and providing insights into how future confirmative research on this topic may be conducted.
摘要：
神经干细胞（NSC）移植是对抗神经退行性疾病的一种新兴且有前途的方法。虽然NSC可以分化为神经细胞类型，许多治疗作用是由旁分泌介导的，“药物样”机制。神经退行性疾病主要是老年人的负担，他们通常患有合并症，因此要接受药物治疗。有关于药物-药物相互作用的大量知识，但几乎没有关于药物治疗对神经干细胞的潜在影响的知识。这些知识对于为个体患者设计量身定制的治疗方案是决定性的。先前的研究表明，抗抑郁药氟西汀和丙咪嗪可能会影响NSC的活力和增殖。这里,我们得出一个假设，关于药物的普遍应用，他汀类药物和抗高血压药，可能会影响NSC的生存能力，扩散,和差异化。我们进行了系统评价和荟萃分析，研究了常用的抗高血压和抗高脂血症药物对NSC功能的潜在影响。根据系统评价和荟萃分析（PRISMA）指南的首选报告项目搜索PubMed和WebofScience数据库。出版物是根据先验确定的相关性选择标准进行评估的。然后对从符合全文审查条件的出版物中提取的数据进行荟萃分析，以评估药物对NSC功能的影响。我们的系统评价确定了1,017项潜在研究，其中55项有资格进行全文审查。其中，21个被包括在定性合成中。对13篇出版物进行了荟萃分析；其余出版物因符合排除标准或缺乏足够的数据进行荟萃分析而被排除。荟萃分析显示，α-2肾上腺素受体激动剂，抗高血压药物类别[p<0.05，95%置信区间(CI)=-1.54；-0.35]，和各种他汀类药物[p<0.05，95％CI=-3.17；-0.0694]对NSC增殖具有抑制作用。此外，我们提供了初步证据，即L型钙通道阻滞剂和他汀类药物，尤其是洛伐他汀,可能会降低NSC的生存能力。尽管文献中可用的数据有限，有明确的迹象表明常用药物的影响，特别是他汀类药物，NSC函数。考虑到各自药物的作用方式，我们揭示了这种影响可能被介导的合理机制，创建一个可测试的假设，并提供对未来如何进行关于这一主题的确认研究的见解。
