Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04896-8
Background The development of vascular calcification (VC) in diabetes is closely related to the endothelial-to-mesenchymal transition (EndMT). We found that microRNA-32-5p (miR-32) was elevated in the plasma of calcification patients. However, it is unclear whether miR-32 mediates the function of bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) in type 2 diabetes (T2D) VC. Methods BMSC-EVs were characterized by TEM, NTA, Western blotting, and confocal microscopy. Alizarin Red and ALP staining assessed the severity of VC. qRT-PCR and Western blotting evaluated the expression of BMP2, RUNX2, GPX4, SLC7A11, VE-cadherin, and N-cadherin, while immunofluorescence was used for detecting VE-cadherin and N-cadherin. In vivo validation was performed using miR-32–/– and ApoE–/– mice. RNA sequencing (RNA-seq) and bioinformatics analysis was conducted to explore underlying mechanisms. Results We demonstrated that BMSC-EVs attenuate VC in endothelial cells (ECs) and inhibit EndMT. In vivo, histological analysis showed that treatment with BMSC-EVs significantly reduced the severity of VC associated with T2D. Notably, knockout of miR-32 further enhanced the inhibitory effect of BMSC-EVs on VC. Mechanistically, transcriptomic and functional analyses suggest that the protective effect of BMSC-EVs on VC is associated with regulation of the MAPK/FoxO signaling pathway, potentially mediated by modulation of ferroptosis. Conclusion These findings demonstrate that BMSC-EVs attenuate T2D-associated VC, partially through miR-32-mediated suppression of EC ferroptosis.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261632
Brain disease treatment is constrained by the blood-brain barrier (BBB), resulting in insufficient drug accumulation in the brain, nonspecific distribution, and immune clearance. Although synthetic nanocarriers improve pharmacokinetics, their long-term stability and biosafety remain uncertain. Plant-derived nanovesicles (PDNVs) have emerged as therapeutic and delivery platforms owing to natural lipid bilayers, biocompatibility, low immunogenicity, and scalability. PDNVs carry lipids, proteins, nucleic acids, and bioactive small molecules, integrating delivery capability with intrinsic therapeutic activity. Component-structure theory interprets multicomponent systems through elemental structure, quantitative-ratio structure, and phase structure. From this perspective, PDNVs are natural composite nanovesicles formed by ordered integration of endogenous components within membrane-confined spaces. This review examines relationships among PDNVs composition, membrane architecture, BBB-crossing delivery, and therapeutic effects in brain diseases, and summarizes engineering strategies for functional optimization. It provides an analytical framework for rational design, quality control, and optimization of PDNVs as central nervous system drug delivery platforms. The review cites experimental evidence including grapefruit-derived nanovesicles for intestinal macrophage targeting, ginger-derived exosomes for glioblastoma, ginseng-derived exosome-like nanoparticles for active BBB penetration, and Momordica charantia small extracellular vesicles mitigating neuronal ferroptosis via GPX4 ubiquitination inhibition in ischemic stroke. These studies demonstrate PDNVs' dual role in preserving endothelial integrity while modulating the tumor microenvironment, and their capacity for nose-to-brain delivery in Parkinson's disease models. The component-structure framework enables systematic engineering of PDNVs for enhanced BBB penetration and therapeutic efficacy.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04896-8
Vascular calcification (VC) in type 2 diabetes (T2D) is driven by endothelial-to-mesenchymal transition (EndMT), yet effective therapies remain elusive. Elevated plasma microRNA-32-5p (miR-32) correlates with calcification, but its role in bone marrow mesenchymal stem cell-derived extracellular vesicle (BMSC-EV) therapy is undefined. We characterized BMSC-EVs by TEM, NTA, Western blotting, and confocal microscopy. Alizarin Red and ALP staining quantified VC severity. qRT-PCR and Western blotting assessed BMP2, RUNX2, GPX4, SLC7A11, VE-cadherin, and N-cadherin; immunofluorescence localized VE-cadherin and N-cadherin. In vivo validation used miR-32–/– and ApoE–/– mice. RNA sequencing and bioinformatics explored mechanisms. BMSC-EVs attenuated VC in endothelial cells (ECs) and inhibited EndMT. In vivo, BMSC-EV treatment significantly reduced T2D-associated VC severity. Notably, miR-32 knockout further enhanced the inhibitory effect of BMSC-EVs on VC. Transcriptomic and functional analyses linked the protective effect to MAPK/FoxO signaling modulation, potentially via ferroptosis regulation. These findings demonstrate that BMSC-EVs attenuate T2D-associated VC, partially through miR-32-mediated suppression of EC ferroptosis, providing a mechanistic foundation for EV-based therapeutics.