A narrative review of spatial multi-omics and organ-on-a-chip technologies for cardio-cerebral-renal crosstalk.

Background: Inter-organ communication within the cardio-cerebral-renal axis orchestrates systemic homeostasis and disease progression. However, conventional methods fail to capture its spatiotemporal complexity; consequently, this creates evidence gaps in dynamic network dissection. Therefore, spatial multi-omics and organ-on-a-chip (OOC) technologies enable unprecedented investigation of these pathways. Objective: We aimed to evaluate the efficacy and safety of spatial multi-omics and organ-on-a-chip (OOC) technologies (intervention) compared to conventional methods (comparator) in decoding cardio-cerebral-renal crosstalk for systemic disorders (population) on outcomes including sensitivity, resolution, and detection accuracy (outcomes). Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov from January 2021 to December 2024. Two reviewers independently screened studies for inclusion. We included 34 studies comprising randomized trials, cohort studies, and preclinical validations. We employed narrative synthesis and random-effects meta-analysis where appropriate. Results: Based on 34 studies involving a substantial number of participants and samples, spatial multi-omics and OOC technologies demonstrated improved sensitivity and better identification of pathogenic networks compared to conventional methods. The findings suggest a consistent trend toward enhanced performance, though heterogeneity across studies was noted. Conclusion: Building on these findings, we conclude that these technologies establish a novel paradigm for decoding multi-organ communication, revealing molecular mechanisms (e.g., exosomal miRNA regulation) and providing clinically actionable biomarkers. However, evidence certainty is moderate due to heterogeneity, thus supporting future precision medicine applications.