2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:Tc1b, Objective This systematic review evaluates the safety, feasibility, tolerability, and efficacy outcomes of intranasally administered stem cells and their derivatives (MSCs, NSCs, secretome, and EVs) for the treatment of neurological and respiratory disorders. Methods A literature search was conducted across PubMed, Google Scholar, Web of Science, Scopus, and ClinicalTrials.gov for published research from January 2011 to December 2025. A total of 19 studies were included (7 published articles, 12 registry-only or grey literature records). Risk of bias was assessed using two complementary Cochrane tools, the RoB 2 tool for all 19 studies and the ROBINS-I tool for the 6 n-RCTs. Sources of heterogeneity were systematically characterized across 5 clinical dimensions, and structural publication bias was evaluated against a 30% registry-only threshold. A random-effects model was selected for pooled analyses, with a planned subgroup analysis of treatment dosage against adverse events. Effect sizes were extracted using SMD, mean differences, risk ratios, and odds ratios as appropriate per outcome type. Results This systematic review was conducted in accordance with PRISMA 2020 guidelines. A total of 104 participants were enrolled in 7 published studies, with one completed registry trial (NCT04602104) confirming actual enrolment of an additional 18 participants. No study achieved an overall low risk of bias under either assessment tool. Under RoB 2, 1 published study was rated as having some concerns, others were rated high risk or some concerns. Under ROBINS-I, 3 n-RCT studies were rated critical overall. The remaining 3 were rated serious. Across the 7 published studies, 98 participants contributed to the analyzed outcomes. Structural publication bias was confirmed. Substantial clinical heterogeneity was identified across 9 conditions, multiple cell product categories, and mixed intranasal and intravenous delivery routes. Conclusion Although current evidence suggests that intranasal administration of stem cells, particularly MSCs and NSCs, in humans is a safe and feasible approach, with possible therapeutic improvements in CNS disorders. However, there is a serious risk of bias, critically small sample sizes, and pervasive publication bias in the available literature. Adequately powered, quadruple-blinded, placebo-controlled randomized trials need to be conducted before clinical translation can be considered. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Neural Stem Cell Therapy: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Neural Stem Cell Therapy (modality). Clinician-written summaries and actionable practice insights. 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Aging Neurosci."],"is-referenced-by-count":0},"unpaywall":{"doi":"10.3389/fnagi.2026.1834543","is_oa":true,"title":"Intranasal administration of stem cells and their derivatives for neurological and respiratory disorders: a systematic review of human clinical trials","updated":"2026-05-13T08:46:39+00:00","published_date":"2026-05-07","best_oa_location":{"url":"https://doi.org/10.3389/fnagi.2026.1834543","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.3389/fnagi.2026.1834543"}}},"created_at":"2026-05-12T13:18:17.986Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"condition","value":"Acute Respiratory Distress Syndrome","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"condition","value":"Amyotrophic Lateral Sclerosis","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"condition","value":"Cerebral Palsy","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"condition","value":"Neurological Disorders","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"condition","value":"Parkinson's Disease","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"condition","value":"Perinatal Arterial Ischemic Stroke","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"condition","value":"Stroke","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"modality","value":"Exosome Therapy","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"modality","value":"Extracellular Vesicle Therapy","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"modality","value":"Mesenchymal Stem Cell Therapy","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"modality","value":"Neural Stem Cell Therapy","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"sample_size","value":"n=104","value_numeric":104},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"study_design","value":"Systematic Review","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"warning","value":"Level of evidence assigned as '3' reflects the systematic review of predominantly non-randomized, high-risk-of-bias studies rather than a review of RCTs; the underlying evidence base is functionally Level 4–5.","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"warning","value":"Several authors are employed by R3 Stem Cell LLC and R3 Medical Research LLC; at least one included study was conducted by a principal investigator who simultaneously served as treating physician and sole outcome assessor under a patient-funded model.","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"warning","value":"The review itself was not pre-registered in PROSPERO, introducing potential analytical flexibility bias at the review level — the authors explicitly acknowledge this.","value_numeric":null},{"paper_doi":"10.3389/fnagi.2026.1834543","tag_type":"warning","value":"The total analyzed sample is only 98 participants across 7 published studies spanning 9 distinct conditions — pooled effect size estimates have very limited interpretability.","value_numeric":null}],"summaries":{"what_studied":"This systematic review evaluated the safety, feasibility, and efficacy of intranasally administered stem cells and their derivatives (MSCs, NSCs, secretome, extracellular vesicles) for neurological and respiratory disorders across 19 studies (7 published, 12 registry-only) from January 2011 to December 2025, covering 104 enrolled participants in published studies.","key_result":"No study achieved low risk of bias under RoB 2 or ROBINS-I; 74% of the 19 studies were rated high risk overall. Structural publication bias was confirmed (63% registry-only or grey literature, exceeding the 30% threshold). Across 98 analyzed participants from 7 published studies, intranasal delivery was consistently reported as safe with no serious adverse events, and preliminary signals of benefit appeared in cerebral palsy, perinatal stroke, and Alzheimer's disease — but no efficacy conclusion is interpretable due to open-label design, absent sham controls, and unblinded outcome assessment in every published trial.","limitations":"- Every published study lacked randomization, sham/placebo intranasal control, and blinded outcome assessment, making efficacy estimates uninterpretable as biological activity.\n- Multiple studies combined intranasal and intravenous delivery, preventing route-specific attribution of any observed effect.\n- The review itself was not pre-registered in PROSPERO, and several authors have direct conflicts of interest (employment by the stem cell manufacturer whose products were evaluated).","practice_takeaway":"Do not adopt intranasal stem cell or exosome therapy for any neurological or respiratory condition based on current evidence — no adequately powered, blinded, sham-controlled trial has been completed or published. The safety signal across ~98 participants is reassuring enough to justify rigorously designed Phase 2 trials, but not clinical use."}}],"initialOffset":1,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Neural Stem Cell Therapy"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Neural Stem Cell Therapy"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Neural Stem Cell Therapy"}}}]]

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