Small Extracellular Vesicles by Nucleus Pulposus Cells Maintain Niche and Cell Homeostasis via Receptor Shuffling and Metabolic Enzyme Supplements

BackgroundSmall extracellular vesicles (sEV) are a conserved mean of communication across the domains of life and lately gained more interest in mammalian non-cancerous work as non-cellular, biological therapeutic with encouraging results in recent studies of chronic degenerative diseases. The nucleus pulposus (NP) is the avascular and aneural center of an intervertebral disc (IVD), home to unique niche conditions and affected in IVD degeneration. We investigated the proteome of autologous and mesenchymal stem cell (MSC) sEVs for their potential to contribute to cell and tissue homeostasis in this niche. MethodsWe aimed to identify characteristics of NP sEVs via mass spectrometric proteome and functional enrichment analysis. We explored the proteome profile of sEVs generated by autologous parent cell lines from bovine coccygeal IVD and adipose tissue, with a focus on NP cells, using adult and fetal donors. We compared these findings to published sEV databases and MSC sEV data. FindingsWe propose several mechanisms associated with NP sEVs: 1. Membrane receptor trafficking to modify signal responses promoting niche homeostasis. 2. Cell homeostasis via proteasome delivery; 3. Redox and energy homeostasis via metabolic enzymes delivery. 4. Immunomodulation beyond an association with a serum protein corona. ConclusionThe proteome signature of sEVs generated by NP parent cells is similar to previously published sEV data, yet with a focus on supplementing anaerobic metabolism and redox balance while contributing to the maintenance of an aneural and avascular microniche.