Translational and Clinical Applications of Dental Stem Cell-Derived Exosomes

Mai, Zizhao; Chen, Huan; Ye, Yu; Hu, Ziyu; Sun, Wenjuan; Cui, Li; Zhao, Xinyuan

doi:10.3389/fgene.2021.750990

Cited by 39 publications

(30 citation statements)

References 85 publications

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“…Increasing evidence has proved that sEVs derived from MSCs could promote the regeneration of skin [ 16 , 17 ], bone [ 18 , 19 ], and cartilage [ 20 , 21 ]. In parallel, the potential clinical application of sEVs derived from dental stem cell in dental tissue regeneration has been shared [ 22 ]. DFSCs conditioned medium was able to provide a favourable microenvironment for self-renewal and osteogenesis of PDLSCs [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Small extracellular vesicles from dental follicle stem cells provide biochemical cues for periodontal tissue regeneration

Rao

Jiang

et al. 2022

Stem Cell Res Ther

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Background Treatments based on stem cell-derived small extracellular vesicles (sEVs) have been explored as an alternative to stem cell transplantation-based therapies in periodontal regeneration. Dental follicle stem cells (DFSCs) have shown great potential for regenerative medicine applications. However, it is unclear whether sEVs derived from DFSCs (DFSCs-sEVs) could be used in periodontal regeneration. This study investigates whether DFSCs-sEVs could regenerate damaged periodontal tissue and the potential underlying mechanism. Methods DFSCs-sEVs were isolated and identified, and periodontal ligament stem cells (PDLSCs) were cocultured with the isolated sEVs. The effect of DFSCs-sEVs on the biological behaviour of PDLSCs was examined using EdU assay, CCK-8 assay, cell cycle analysis, wound healing, alizarin red staining, qRT-PCR, and western blot analysis. RNA sequencing and functional enrichment analysis were used to detect the signal pathway involved in the effect of DFSCs-sEVs on PDLSCs. PDLSCs were pretreated with ERK1/2 or p38 MAPK inhibitors to investigate the possible involvement of the ERK1/2 and p38 MAPK pathways. Additionally, DFSCs-sEVs were combined with collagen sponges and transplanted into the periodontal defects in SD rats, and then, pathological changes in periodontal tissue were examined using haematoxylin and eosin (HE) staining and micro-CT. Results PDLSCs could internalize DFSCs-sEVs, thereby enhancing the proliferation assessed using EdU assay, CCK-8 assay and cell cycle analysis. DFSCs-sEVs significantly enhanced the migration of PDLSCs. DFSCs-sEVs promoted osteogenic differentiation of PDLSCs, showing deep Alizarin red staining, upregulated osteogenic genes (RUNX2, BSP, COL1), and upregulated protein expression (RUNX2, BSP, COL1, ALP). We found that p38 MAPK signalling was activated via phosphorylation. Inhibition of this signalling pathway with a specific inhibitor (SB202190) partially weakened the enhanced proliferation. After DFSCs-sEVs transplantation, new periodontal ligament-like structures and bone formation were observed in the damaged periodontal area in rats. Labelled DFSCs-sEVs were observed in the newly formed periodontal ligament and soft tissue of the defect area. Conclusions Our study demonstrated that DFSCs-sEVs promoted periodontal tissue regeneration by promoting the proliferation, migration, and osteogenic differentiation of PDLSCs. The effect of DFSCs-sEVs in promoting PDLSCs proliferation may be partially attributed to the activation of p38 MAPK signalling pathway. DFSCs-sEVs provide us with a novel strategy for periodontal regeneration in the future.

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Section: Introductionmentioning

confidence: 99%

Small extracellular vesicles from dental follicle stem cells provide biochemical cues for periodontal tissue regeneration

Rao

Jiang

et al. 2022

Stem Cell Res Ther

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“…At present, an increasing number of studies have shown that exosomes play a key role in the growth, metastasis, and drug resistance of various cancer cells ( Cheng et al, 2019 ; Mai et al, 2021 ). Our study screened exosome-related lncRNAs related to prognosis and constructed a prognosis-related lncRNA risk model for liver cancer patients.…”

Section: Discussionmentioning

confidence: 99%

A prognostic exosome-related LncRNA risk model correlates with the immune microenvironment in liver cancer

Zhang

et al. 2022

Front. Genet.

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Background: Emerging studies have shown the important roles of long noncoding RNAs (lncRNAs) in the occurrence and development of liver cancer. However, the exosome-related lncRNA signature in liver cancer remains to be clarified.Methods: We obtained 371 tumor specimens and 50 normal tissues from the TCGA database. These samples were randomly divided into the training queue and verification queue. The exosome-related lncRNA risk model was verified by correlation analysis, Lasso regression analysis, and Cox regression analysis. The differences in the immune microenvironment in the two risk groups were obtained by analyzing the infiltration of different immune cells.Results: Five exosome-related lncRNAs associated (MKLN1-AS, TMCC1-AS1, AL031985.3, LINC01138, AC099850.3) with a poor prognosis were identified and used to construct the signature. Receiver operating curve (ROC) and survival curves were used to confirm the predictive ability of this signature. Based on multivariate regression analysis in the training cohort (HR: 3.033, 95% CI: 1.762–5.220) and validation cohort (HR: 1.998, 95% CI: 1.065–3.751), the risk score was found to be an independent risk factor for patient prognosis. Subsequently, a nomogram was constructed to predict the 1-, 3-, 5-years survival rates of liver cancer patients. Moreover, this signature was also related to overexpressed immune checkpoints (PD-1, B7-H3, VSIR, PD-L1, LAG3, TIGIT and CTLA4).Conclusion: Our study showed that exosome-related lncRNAs and the corresponding nomogram could be used as a better index to predict the outcome and immune regulation of liver cancer patients. This signature might provide a new idea for the immunotherapy of liver cancer in the future.

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“…hDPSCs can also release hDPSC-EVs, including exosomes and microvesicles, into hDPSC-CM [ 35 , 62 , 74 ]. hDPSC-EVs are packed within a lipid bilayer membrane.…”

Section: Action Of Evs Released From Hdpscs (Hdpsc-evs)mentioning

confidence: 99%

A New Target of Dental Pulp-Derived Stem Cell-Based Therapy on Recipient Bone Marrow Niche in Systemic Lupus Erythematosus

Sonoda

Yamaza

2022

IJMS

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Recent advances in mesenchymal stem/stromal cell (MSC) research have led us to consider the feasibility of MSC-based therapy for various diseases. Human dental pulp-derived MSCs (hDPSCs) have been identified in the dental pulp tissue of deciduous and permanent teeth, and they exhibit properties with self-renewal and in vitro multipotency. Interestingly, hDPSCs exhibit superior immunosuppressive functions toward immune cells, especially T lymphocytes, both in vitro and in vivo. Recently, hDPSCs have been shown to have potent immunomodulatory functions in treating systemic lupus erythematosus (SLE) in the SLE MRL/lpr mouse model. However, the mechanisms underlying the immunosuppressive efficacy of hDPSCs remain unknown. This review aims to introduce a new target of hDPSC-based therapy on the recipient niche function in SLE.

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Translational and Clinical Applications of Dental Stem Cell-Derived Exosomes

Cited by 39 publications

References 85 publications

Small extracellular vesicles from dental follicle stem cells provide biochemical cues for periodontal tissue regeneration

Small extracellular vesicles from dental follicle stem cells provide biochemical cues for periodontal tissue regeneration

A prognostic exosome-related LncRNA risk model correlates with the immune microenvironment in liver cancer

A New Target of Dental Pulp-Derived Stem Cell-Based Therapy on Recipient Bone Marrow Niche in Systemic Lupus Erythematosus

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