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The Role of Mesenchymal Stromal Cells-Derived Small Extracellular Vesicles in Diabetes and Its Chronic Complications

ABSTRACT: Mesenchymal stromal cells (MSCs) are applied in regenerative medicine of several tissues and organs nowadays by virtue of their self-renewal capabilities, multiple differentiation capacity, potent immunomodulatory properties, and their ability to be favourably cultured and manipulated. With the continuous development of “cell-free therapy” research, MSC-derived small extracellular vesicles (MSC-sEVs) have increasingly become a research hotspot in the treatment of various diseases. Small extracellular vesicles (SEVs) are membrane vesicles with diameters of 30 to 150 nm that mediate signal transduction between adjacent or distal cells or organs by delivering non-coding RNA, protein, and DNA. The contents and effects of sEVs vary depending on the properties of the originating cell. In recent years, MSC-sEVs have been found to play an important role in the occurrence and development of diabetes mellitus as a new way of communication between cells. Diabetes mellitus is a common metabolic disease in clinic. Its complications of the heart, brain, kidney, eyes, and peripheral nerves are a serious threat to human health and has been a hot issue for clinicians. MSC-sEVs could be applied to repair or prevent damage from the complications of diabetes mellitus through anti-inflammatory effects, reduction of endoplasmic reticulum-related protein stress, polarization of M2 macrophages, and increasing autophagy. Therefore, we highly recommend that MSC-sEVs-based therapies to treat diabetes mellitus and its chronic complication be further explored. The analysis of the role and molecular mechanisms of MSC-sEVs in diabetes and its related complications will provide new idea and insights for the prevention and treatment of diabetes.

SUBMITTER: Li F

PROVIDER: S-EPMC8721875 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEquine adipose-derived mesenchymal stromal cells (e-AdMSC) exhibit attractive proregenerative properties strongly related to the delivery of extracellular vesicles (EVs) that enclose different kinds of molecules including RNAs. In this study, we investigated small RNA content of EVs produced by e-AdMSC with the aim of speculating on their possible biological role.MethodsEVs were obtained by ultracentrifugation of the conditioned medium of e-AdMSC of 4 subjects. Transmission electron microscopy and scanning electron microscopy were performed to assess their size and nanostructure. RNA was isolated, enriched for small RNAs (<200 nt), and sequenced by Illumina technology. After bioinformatic analysis with state-of-the-art pipelines for short sequences, mapped reads were used to describe EV RNA cargo, reporting classes, and abundances. Enrichment analyses were performed to infer involved pathways and functional categories.ResultsElectron microscopy showed the presence of vesicles ranging in size from 30 to 300 nm and expressing typical markers. RNA analysis revealed that ribosomal RNA was the most abundant fraction, followed by small nucleolar RNAs (snoRNAs, 13.67%). Miscellaneous RNA (misc_RNA) reached 4.57% of the total where Y RNA, RNaseP, and vault RNA represented the main categories. miRNAs were sequenced at a lower level (3.51%) as well as protein-coding genes (1.33%). Pathway analyses on the protein-coding fraction revealed a significant enrichment for the "ribosome" pathway followed by "oxidative phosphorylation." Gene Ontology analysis showed enrichment for terms like "extracellular exosome," "organelle envelope," "RNA binding," and "small molecule metabolic process." The miRNA target pathway analysis revealed the presence of "signaling pathways regulating pluripotency of stem cells" coherent with the source of the samples.ConclusionWe herein demonstrated that e-AdMSC release EVs enclosing different subsets of small RNAs that potentially regulate a number of biological processes. These findings shed light on the role of EVs in the context of MSC biology.

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The Role of Mesenchymal Stromal Cells-Derived Small Extracellular Vesicles in Diabetes and Its Chronic Complications

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