AF cell derived exosomes regulate endothelial cell migration and inflammation: Implications for vascularization in intervertebral disc degeneration

Exosomes Immunity Strategy: A Novel Approach for Ameliorating Intervertebral Disc Degeneration

“… Strassburg et al (2012) also reported that the formation of gap junctions and cell fusion are not the predominant mechanisms of interaction; intercellular transfer of membrane components is the main interactive mechanism between BMSCs and NP cells. These findings indicate that direct injection of BMSCs into IVD is not effective compared to injection of NP exosomes into IVD, which is consistent with the finding of Sun et al (2021) that indirect cell–cell communication and paracrine are predominant in keeping the avascular condition of IVD. However, the detailed interactive mechanisms between BMSC and NP cells remain unclear, and more specific components like proteins, miRNAs, transcription factors, and lipids are expected for further research.…”

“… Pohl et al (2016) have discovered that endothelial microparticles secreted from vascular endothelial cells enhance MMP expression in AF cells, suggesting that the vascular endothelial cells could act on AF cells through microparticle delivery, and it could help blood vessel ingrowth into IVD by promoting ECM catabolism. Together with the findings that degenerative AF cells affect vascularization of vascular endothelial cells by delivering AF exosomes ( Sun et al, 2021 ). Both AF and vascular endothelial cells secrete microparticles like exosomes, and they endocytose microparticles secreted from each other, and these reports all display the essential roles of microparticles/exosomes in AF and blood vessel communication.…”

“…Blood vessel invasion would cause activation of immunocytes and inflammatory factors, increase neuralization, and thereby damage the dynamic balance in IVD (Sun et al, 2020b). Existing studies have reported the pivotal roles of exosomes in inhibiting the growth of blood vessels; Cornejo et al (2015) and Kwon et al (2017) have found that soluble factors from notochordal cells could suppress endothelial cell invasion and vessel formation by inhibiting the VEGF signaling pathway; meanwhile, Sun et al (2020b) have confirmed the finding that notochordal cell-derived exosomes could suppress proliferation of HUVECs; another research has also discovered the regulatory roles of AF exosomes, showing that degenerative AF exosomes promote migration of HUVECs and upregulate the expression of inflammatory factors (Sun et al, 2021). Furthermore, Liang et al (2017) have reported that the co-culture system between PMSCs and endothelial progenitor cells (EPCs) enhances the angiogenic potential of EPCs through PDGF and the Notch signaling pathway (Komaki et al, 2017).…”

“…Vascularization has been widely observed in IDD and has been considered as a pathological feature, which mainly occurs in AF tissue, and blood vessels grow and infiltrate inwards, could cause NP tissue exposure to immune system, and thereby damage immune privilege of IVD ( Kim et al, 1981 ; Di Martino et al, 2013 ). Sun et al (2021) have verified that the exosomes could be released by both degenerated and non-degenerated AF cells; they could also be internalized by HUVECs, and degenerative AF exosomes could enforce HUVEC migration faster than non-degenerative AF exosomes, elucidating that degenerative AF cells could induce IVD vascularization via exosome-mediated effects, while non-degenerative AF tissues could suppress blood vessels ingrowth as a physical barrier, and its exosomes could also be regarded as an angiogenesis inhibitor to maintain the healthy avascular condition of IVD. These results imply that AF exosomes could serve as one of the mediators in intercellular communication of IVD and modulate the vascularization of IVD.…”

Mesenchymal Stem Cell-Derived Exosomes: The New Frontier for the Treatment of Intervertebral Disc Degeneration

“…Indeed, IVD repair may be promoted by CEP stem cell exosomes by inhibiting NPC apoptosis and encouraging the migration of CEP stem cells into the IVD and differentiate into NPCs via autocrine mechanisms [117,118]. AF-derived exosomes have also showed a protective effect in IDD [120]. Aging and degenerative tissues usually accumulate in endoplasmic reticulum (ER) advanced glycation end-products (AGEs) related to inflammation, cell death, metabolic dysfunction, and stress [122,123].…”