用于神经系统疾病的再生生物制剂经鼻给药：临床研究的系统综述。
完整摘要 · 中文译文
引言：鼻内递送是一种微创途径，可将再生生物制剂递送至中枢神经系统，同时绕过血脑屏障。该方法在多种神经系统疾病中的人体临床证据仍分散于多个疾病领域、生物制剂类别、给药框架和递送方法之中，限制了领域层面的综合。本研究旨在系统评价鼻内再生生物制剂在神经系统疾病患者中的安全性、给药特征、递送方法异质性及疾病特异性效应方向，包括间充质基质细胞（MSCs）、神经干细胞（NSCs）、外泌体、分泌组和条件培养基、母乳来源生物制剂及相关再生制品。 方法学：开展了一项在国际前瞻性系统评价注册库（PROSPERO）注册的系统评价，并按照系统评价和荟萃分析优先报告条目（PRISMA 2020）指南进行报告，综合采用无荟萃分析综合（SWiM）建议进行。检索PubMed、Google Scholar、ClinicalTrials.gov和ChiCTR，时间范围为2015年1月至2026年8月。采用与研究设计相适应的经验证工具评估偏倚风险（RoB），包括Cochrane RoB 2和non-randomized studies - of Interventions偏倚风险（ROBINS-I），并使用Joanna Briggs Institute（JBI）病例系列关键评价清单评估无对照研究的方法学质量。 病例报告。 结果：共纳入16篇出版物，涵盖12种神经系统疾病中的18个患者队列。未报告与治疗相关的严重不良事件。大多数队列显示临床改善，其中一个队列报告病情稳定，但以非对照设计为主意味着无法排除安慰剂反应和自然疾病史的影响。然而，生物学类别与疾病适应证存在强烈混杂，给药方案异质且不可比较，并且使用了五种递送技术。 讨论：通过整合跨生物学类别和神经系统疾病的临床证据，本综述明确了当前的安全性概况，突出了主要的方法学空白，并为未来标准化的鼻内再生试验提供了框架。 结论：在考虑临床采用之前，需要进行足够把握度、标准化和对照的试验。
完整摘要 · 英文原文
INTRODUCTION: Intranasal delivery is a minimally invasive route for administering regenerative biologics to the central nervous system while bypassing the blood-brain barrier. Human clinical evidence for this approach across neurological disorders remains dispersed across multiple disease areas, biologic classes, dosing frameworks, and delivery methods, limiting field-level synthesis. This study was conducted to systematically evaluate the safety, dosing characteristics, delivery method heterogeneity, and disease-specific direction of effect of intranasal regenerative biologics, including mesenchymal stromal cells (MSCs), neural stem cells (NSCs), exosomes, secretome and conditioned medium, breast milk-derived biologic preparations, and related regenerative products, in patients with neurological disorders. METHODOLOGY: An International Prospective Register of Systematic Reviews (PROSPERO)-registered systematic review was conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines, with synthesis performed in accordance with Synthesis Without Meta-Analysis (SWiM) recommendations. PubMed, Google Scholar, ClinicalTrials.gov, and ChiCTR were searched from January 2015 to August 2026. Risk of Bias (RoB) was assessed using study design-appropriate validated tools, including Cochrane RoB 2 and Risk of Bias In Non-randomized Studies - of Interventions (ROBINS-I) and methodological quality of uncontrolled studies was appraised using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists for Case Series and Case Reports. RESULTS: Sixteen publications comprising 18 patient cohorts across 12 neurological conditions were included. No treatment-related serious adverse events were reported. Most cohorts showed clinical improvement, while one reported stabilization, though the predominantly uncontrolled designs mean placebo response and natural disease history cannot be ruled out. However, the biologic class was strongly confounded by disease indication, dosing was heterogeneous and non-comparable, and five delivery techniques were used. DISCUSSION: By integrating clinical evidence across biologic classes and neurological disorders, this review defines the current safety landscape, highlights major methodological gaps, and provides a framework for standardized future intranasal regenerative trials. CONCLUSION: Adequately powered, standardized, and controlled trials are required before clinical adoption can be considered.