Wawid Purwatiningsih, Fedik Abdul Rantam, Aulanni’am Aulanni’am, Heri Prayitno
Background: Organ inflammatory diseases remain a major contributor to global morbidity and mortality, yet current therapies fail to adequately prevent tissue damage progression. Stem cell therapy offers immunomodulatory and regenerative benefits, but its effectiveness varies substantially across administration routes, creating uncertainty in optimal clinical selection. Main body: This systematic literature review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to compare administration routes of stem cell therapy and its derivatives for organ inflammation. Searches of Scopus, Web of Science, and PubMed databases up to 4 July 2025 identified 790 records; after screening and quality appraisal with Mixed Methods Appraisal Tool (MMAT) 2018, 57 empirical studies published from 2015 onward were included, covering 17 administration routes evaluated against 10 predefined effectiveness and safety domains. Qualitative findings were converted into an ordinal 1–3 scoring system and visualized in a heatmap to enable semiquantitative comparison across routes. Invasive routes such as intramyocardial, intra-arterial, portal vein, intrathecal, and intraparenchymal delivery consistently achieved the highest composite scores for target organ retention, homing, and functional repair, but were penalized for procedure-related risks and feasibility. Noninvasive routes (intravenous, intranasal, nebulized, oral, and sublingual/topical) showed lower target retention but more favorable safety, practicality, and suitability for repeated dosing. Across indications, intraperitoneal delivery tended to outperform intravenous administration for abdominal diseases, whereas intranasal and nebulized approaches were particularly promising for nose-to-brain and lung targeting using relatively low doses. Conclusion: Stem cell therapy effectiveness is route-specific and reflects trade-offs between target organ delivery and safety–feasibility profiles. The semiquantitative synthesis presented here supports a “route-specific optimization” framework to guide personalized selection of administration routes and to prioritize future translational and clinical research. © The Author(s) 2025.
Doctoral Program in Veterinary Science, Faculty of Veterinary Medicine Universitas Airlangga, Mulyorejo C-Campus of Unair, East Java, Surabaya, 60115, Indonesia; Faculty of Veterinary Medicine, Universitas Airlangga, Mulyorejo C-Campus of Unair, East Java, Surabaya, 60115, Indonesia; Faculty of Science, Universitas Brawijaya, Jl. Veteran, Ketawanggede, Lowokwaru, East Java, Malang, 65145, Indonesia; Faculty of Veterinary Medicine, Universitas Brawijaya, Puncak Dieng Eksklusif, Kalisongo, Dau, East Java, Malang, 65151, Indonesia; Library, Universitas Brawijaya, Jl. Veteran, Ketawanggede, Lowokwaru, East Java, Malang, 65145, Indonesia
