Work

3D spheroids of umbilical cord-derived MSCs protect retinal pigment epithelium against oxidative and inflammatory injury by activating autophagy

Year: 2026

Type: article

Abstract: BACKGROUND: Age-related macular degeneration (AMD) is characterized by progressive retinal pigment epithelium (RPE) dysfunction driven by oxidative stress and chronic inflammation, in which NLRP3 inflammasome activation plays a critical role. Mesenchymal stem cells (MSCs) exhibit therapeutic potential, but their efficacy is limited by poor survival and reduced paracrine activity in hostile microenvironments. Here, we investigated whether three-dimensional (3D) spheroid culture enhances the protective effects of umbilical cord-derived MSCs (UC-MSCs) on RPE cells by promoting autophagy and suppressing inflammasome activation. METHODS: )-induced oxidative injury models both in vitro and in vivo. Retinal morphology and function were assessed via histology and electroretinography, while NLRP3/caspase-1 activation, LC3-II/I ratios, and autophagy flux were quantified using immunofluorescence and Western blot. GO/KEGG enrichment was performed to identify pathways associated with 3D MSCs efficacy. Mechanistic involvement of autophagy was validated using 3-methyladenine (3-MA) and rapamycin. RESULTS: -induced injury. In vivo, 3D MSC treatment preserved retinal structure, reduced RPE cell loss, and improved retinal function. In vitro, co-culture with 3D MSCs markedly improved ARPE-19 viability, reduced apoptosis, and modulated autophagy-related marker expression, as evidenced by increased LC3-II/I ratios. 3D MSCs significantly inhibited NLRP3 inflammasome activation and pro-inflammatory cytokine release, effects reversed by 3-MA and further enhanced by rapamycin. CONCLUSIONS: 3D spheroid culture substantially augments the therapeutic efficacy of UC-MSCs by boosting autophagy and suppressing NLRP3 inflammasome signaling, resulting in enhanced protection of RPE cells from oxidative and inflammatory injury. These findings provide preclinical evidence supporting 3D MSCs as a promising therapeutic strategy for AMD.

Source: Stem Cell Research & Therapy

DOI: 10.1186/s13287-026-05043-z

Authors: Qian Xu, Mengyao Li, Dong Li, Xiaoyu Dai, Yifei Zhang, Yi Qu

Institutions: Shandong University, Qilu Hospital of Shandong University, Shandong First Medical University, Jinan Central Hospital

Language: English

Topic: Mesenchymal stem cell research

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,190