Extracellular Vesicles Derived from Human Gingival Mesenchymal Stem Cells: A Transcriptomic Analysis

Abstract

Human gingival mesenchymal stem cells (hGMSCs) have outstanding characteristics of proliferation and are able to differentiate into osteogenic, chondrogenic, adipogenic, and neurogenic cell lineages. The extracellular vesicles (EVs) secreted by hGMSCs contain proteins, lipids, mRNA and microRNA have emerged as important mediators of cell-to-cell communication. In this study, we analyzed the transcriptome of hGMSCs-derived EVs using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 26 structural protein classes and the presence of “non-coding RNAs”. Our results showed that EVs contain several growth factors such as Transforming Growth Factor-β (TGF-β), Fibroblast Growth Factor (FGF), and Vascular Endothelial Growth Factors (VEGF) implicated in osteoblast differentiation and in angiogenetic process. Furthermore, the transcriptomic analysis showed the presence of glial cell-derived neurotrophic factor (GDNF) family ligands and neurotrophins involved in neuronal development. The NGS analysis also identified the presence of several interleukins among which some with anti-inflammatory action. Moreover, the transcriptome profile of EVs contained members of the Wnt family, involved in several biological processes, such as cellular proliferation and tissue regeneration. In conclusion, the huge amount of growth factors included in the hGMSCs-derived EVs could make them a big resource in regenerative medicine.

Mesenchymal stem cell exosomes in bone regenerative strategies—a systematic review of preclinical studies

“…This multifaceted mechanism of action of MSC exosomes in bone regeneration could be attributed to the rich diverse cargo of nucleic acids, proteins, and lipids [ 67 , 69 ]. Given the well-established immunomodulatory properties of MSCs, previous transcriptomics and proteomics profiling of MSC EVs/exosomes have also revealed an enrichment of growth factors and cytokines involved in immunomodulation [ [70] , [71] , [72] , [73] ]. However, in the 23 studies reviewed [ [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] ], none have examined the immunomodulatory effects of MSC exosomes on bone regeneration.…”

Functional Relationship between Osteogenesis and Angiogenesis in Tissue Regeneration

“…These cells are derived from neural crests and are a transitory group of embryonic pluripotent stem cells that migrate from the lateral margins of the neural plate toward different tissues. The significance of this reservoir is associated to its easy obtainability and to the considerable numbers of oral tissues from which stem cells can be isolated and characterized [30]. Up to the present time, diverse human oral stem cells have been reported in the literature: human Dental Pulp Stem Cells (hDPSCs), human Exfoliated Deciduous Teeth Stem Cells (SHED), human Periodontal Ligament Stem Cells (hPDLSCs), human Apical Papilla Stem Cells (hAPSCs), human Dental Follicle Stem Cells (hDFSCs) and human Gingival Mesenchymal Stem Cells (hGMSCs) ( Figure 2) [31,32].…”

“…EVs derived from MSCs showed paracrine effects without the direct use of living cells in order to avoid ethical concerns and the limitations in administering living cells. The main advantages in the use of EVs regard their safety and manipulation [30]. The functions of EVs in bone metabolism and bone regeneration have been widely reported in the recent literature [72].…”

Stem Cells Secretome from Oral Tissue Could Represent a Promising Therapeutic Approach in COVID-19-Disease?

“…Moreover, the latest in vitro and in vivo studies on hOTSCs produced, not only a large quantity of cytokines, but also extracellular vesicles (EVs) with high content of anti-inflammatory mediators, which were important for the therapeutic strategy in several diseases [ 20 , 21 ], other than the regenerative capacity in the damaged tissues [ 22 , 23 ].…”