Background: Retinal degeneration remains one of the predominant causes of blindness, with extremely low regenerative capacity in the mammalian retina. Stem cell-based therapy is a highly promising approach for retinal regeneration, but efficient stem cell migration and integration are significant challenges. This systematic review aimed to discuss chemokine-directed stem cell migration in retinal regeneration, summarising important chemokines, signalling pathways, and therapeutic opportunities.
Methods: A systematic literature search was done in PubMed, Embase, Scopus, Web of Science, Cochrane Library, CINAHL, and PsycINFO between January 2010 and January 2025. Preclinical and clinical studies that explored chemokine-stimulated stem cell migration during retinal repair were included based on the inclusion criteria. The data extracted included chemokine-receptor interaction, signalling pathways, type of stem cells, route of delivery, and outcomes of retinal repair. The ROBINS-I tool was used to evaluate the risk of bias.
Results: In 384 studies, 12 were included. The SDF-1/CXCL12-CXCR4 pathway was explored in the most detail, augmenting stem cell homing and integration. Other pathways, such as ERK/MAPK, PI3K/Akt, and JAK-STAT, also played a role in migration and survival. Chemokine-modulated therapies enhanced retinal function and repair, but immune responses and delivery issues remain. New approaches such as biodegradable scaffolds, magnetic targeting, and chemically engineered chemokines were discovered to optimise stem cell localisation and efficacy.
Conclusion: Chemokine-directed stem cell migration is an exciting field for retinal regeneration, which has the potential to improve targeted cell delivery and integration. While SDF-1/CXCL12 remains the gold standard, other pathways and new delivery pathways are also extremely capable. Augmenting chemokine-based therapies, overcoming immunological barriers, and translating them into the clinic in the future will be paramount to optimising stem cell-mediated retinal repair.
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Review Article |
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Microbiome in Cancer Received: 2025/07/24 | Accepted: 2025/09/11 | Published: 2025/09/30