Decoding Mesenchymal Stem Cell Homing to Inflamed Organs: A Cross-Organ Systematic Review of Cytokine Gradients, Chemokines, and Surface Receptors

Chronic inflammatory diseases contribute substantially to global mortality and demand cell-based therapeutic strategies that are not only immunomodulatory but also capable of precise, stable, and sustained homing to target organs, while mechanistic evidence across organs remains fragmented. This study aimed to synthesize empirical evidence on the mechanisms by which mesenchymal stem cells (MSCs) sense inflammatory signals, the key cytokines/ chemokines involved, and the surface receptors that regulate homing to inflamed organs. A systematic literature review was conducted using a Population, Intervention, Comparison, Outcome (PICO) framework using Scopus, Web of Science, and ScienceDirect databases, with standardised keywords. Study selection was facilitated by Parsif.al, applying predefined inclusion–exclusion criteria and methodological quality assessment using the Mixed Methods Appraisal Tool (MMAT 2018), followed by structured data extraction and narrative thematic synthesis. From 168 records, 57 experimental studies were included. These indicate that MSC homing is predominantly governed by the SDF-1/ CXCL12–CXCR4 axis, which is potentiated by hypoxic and inflammatory conditions, alongside the roles of IL-1, IL-6, TNF-α, IFN-γ, IL-10, TGF-β, CCL2, chemerin, and CCL5, and the secretion of VEGF, HGF, TSG-6, and MMPs for tissue repair and matrix remodelling. Receptors including CXCR4, CXCR7, CCR2, CXCR1, CCR1, ChemR23, integrins, ICAM-1, VCAM-1, CD44/HCELL, PDGFR, and c-Met shape an organ-specific “homing signature”. The concept of MSC “homing competence” supports the design of preconditioning strategies, route selection, and receptor engineering to achieve safer, more effective, clinically translatable and personalised therapies for inflammatory diseases.