Human Oral Stem Cells, Biomaterials and Extracellular Vesicles: A Promising Tool in Bone Tissue Repair

Trubiani, Oriana; Marconi, Guya Diletta; Pierdomenico, Sante D.; Piattelli, Adriano; Diomede, Francesca; Pizzicannella, Jacopo

doi:10.3390/ijms20204987

Cited by 94 publications

(73 citation statements)

References 78 publications

(91 reference statements)

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“…The utilization of sEVs for both therapeutic and diagnostic applications is a rapidly developing field, with continual refinement of isolation methods. In particular, stem cell-derived sEVs have been explored as a promising cell-free regenerative medicine strategy for bone tissue engineering [27,28]. The two published studies reporting on salivary sEV research in the periodontal field used a precipitation-based ExoQuick kit [17,18], which has the potential to produce protein and nucleic acid contamination [29].…”

Section: Discussionmentioning

confidence: 99%

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status—A Pilot Study

Han

Bartold

Salomón

et al. 2020

IJMS

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This pilot study aims to investigate whether salivary small extracellular vesicle (sEV)-associated microRNAs could act as potential biomarkers for periodontal disease status. Twenty-nine participants (10 who were healthy, nine with gingivitis, 10 with stage III/IV periodontitis) were recruited and unstimulated whole saliva samples were collected. Salivary sEVs were isolated using the size-exclusion chromatography (SEC) method and characterised by morphology, EV-protein and size distribution using transmission electron microscopy (TEM), Western Blot and Nanoparticle Tracking Analysis (NTA), respectively. Ten mature microRNAs (miRNAs) in salivary sEVs and saliva were evaluated using RT-qPCR. The discriminatory power of miRNAs as biomarkers in gingivitis and periodontitis versus healthy controls was evaluated by Receiver Operating Characteristics (ROC) curves. Salivary sEVs were comparable to sEVs morphology, mode, size distribution and particle concentration in healthy, gingivitis and periodontitis patients. Compared to miRNAs in whole saliva, three significantly increased miRNAs (hsa-miR-140-5p, hsa-miR-146a-5p and hsa-miR-628-5p) were only detected in sEVs in periodontitis when compared to that of healthy controls, with a good discriminatory power (area under the curve (AUC) = 0.96) for periodontitis diagnosis. Our study demonstrated that salivary sEVs are a non-invasive source of miRNAs for periodontitis diagnosis. Three miRNAs that are selectively enriched in sEVs, but not whole saliva, could be potential biomarkers for periodontal disease status.

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Section: Discussionmentioning

confidence: 99%

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status—A Pilot Study

Han

Bartold

Salomón

et al. 2020

IJMS

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“…In recent years, a great deal of attention has been paid to the application of not only allogeneic but also xenogeneic sEV in various fields, such as therapeutic target, [30][31][32] diagnosis tools, 33 drug/gene delivery vector 34 and inducer of tissue regeneration. [35][36][37] Although the highly attractive features of sEV, such as the absence of immunogenicity, natural composition, and the ability to be loaded with small molecules and biologics, 38 the use of sEV derived from xenogeneic tissue in clinical applications remained limited because it was still unclear whether sEV derived from different species would have an impact on their therapeutic effects.…”

Section: Discussionmentioning

confidence: 99%

<p>Comparison of the Therapeutic Effect of Allogeneic and Xenogeneic Small Extracellular Vesicles in Soft Tissue Repair</p>

Dong

Wu²,

Zhang

et al. 2020

IJN

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Small extracellular vesicles (sEV) are a heterogeneous group of vesicles that consist of proteins, lipids and miRNA molecules derived from the cell of origin. Although xenogeneic sEV have been applied for soft tissue regeneration successfully, the regeneration effect of allogeneic and xenogeneic sEV has not been compared systematically. Methods: Our previous study has shown that sEV derived from rat adipose tissue successfully induced neoadipose regeneration. In this study, sEV were isolated from rat adipose tissue (r-sEV-AT) and porcine adipose tissue (p-sEV-AT), the morphology, size distribution and marker proteins expression of r-sEV-AT and p-sEV-AT were characterized. Besides, the sEV/AT ratio was evaluated and compared between r-sEV-AT and p-sEV-AT. Rat adipose-derived stromal/ stem cells (rASCs) and rat aorta endothelial cells (rECs) were adopted to test the cellular response to allogeneic and xenogeneic sEV-AT. The effects of allogeneic and xenogeneic sEV-AT on host cells migration and neoadipose formation were evaluated in a subcutaneous customdesigned model. A full-thickness skin wound healing model was used to further compare the ability of allogeneic and xenogeneic sEV-AT in inducing complex soft tissue regeneration. Results: p-sEV-AT showed similar morphology and size distribution to r-sEV-AT. Marker proteins of sEV were detected in both r-sEV-AT and p-sEV-AT. The sEV/AT ratio of porcine was slightly higher than that of rat. The effects of r-sEV-AT and p-sEV-AT on the differentiation of rASCs and rECs showed no significant difference. When allogeneic and xenogeneic sEV-AT were subcutaneously implanted into the back of SD rats, the host cells chemotactic infiltration was observed in 1 week and neoadipose tissue formation was induced in 8 weeks; no significant difference was observed between allogeneic and xenogeneic sEV-AT. For complex soft tissue regeneration, both allogeneic and xenogeneic sEV-AT significantly promoted wound re-epithelialization, granulation tissue formation and hair follicle regeneration and then accelerated skin wound healing. Conclusion: Our results demonstrated that sEV derived from the same tissues of different species might be loaded with similar therapeutic substance benefitting tissue repair and regeneration, and paved the way for future research aimed at xenogeneic sEV application.

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“…Periodontal ligament -derived stem cells were used to treat PD in humans (clinical trial identi er: NCT02523651). Apart from oral stem cells, other regenerative approaches such as the use of biomaterials, by themselves or used as scaffolds to load cells or drugs, extracellular vesicles, hold promising therapeutic future to repair and grow bone [71,72]. Nevertheless, additional studies are needed to determine the bene cial effects of using dental-derived stem cells and LLP2A-Ale for PD-induced bone loss.…”

Section: Discussionmentioning

confidence: 99%

A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation

Jiang

Liu

et al. 2020

Preprint

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Aims. Currently, there are no effective medications that reverse periodontal disease (PD)-induced bone loss. The objective of this study was to test a new anabolic compound, LLP2A-Ale, or with the combination treatment of mesenchymal stromal cell (MSC), in the treatment of bone loss secondary to PD. Materials and Methods. PD was induced in mice by placing a ligature around the second right molar. At one week after disease induction, the mice were treated with placebo, LLP2A-Ale, MSCs, or combination of LLP2A-Ale + MSCs, and euthanized at week 4. Results. We found that PD induced alveolar bone loss that was associated with reduced bone formation. LLP2A alone and in combination with MSCs sustained alveolar bone formation and reversed alveolar bone loss. Additionally, PD alone caused systemic inflammation and increased the circulating levels of G-CSF, IP-10, MIP-1a, and MIP2, which were suppressed by LLP2A-Ale +/- MSCs. LLP2A-Ale +/- MSCs increased bone formation at the peripheral skeletal site (distal femur), which was otherwise suppressed by PD. Conclusion. Our findings indicated that LLP2A-Ale treatment rescued alveolar bone loss caused by PD, primarily by increasing bone formation. LLP2A-Ale also attenuated the circulating levels of a series of inflammatory cytokines and reversed the PD-induced suppression of systemic bone formation.

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Human Oral Stem Cells, Biomaterials and Extracellular Vesicles: A Promising Tool in Bone Tissue Repair

Cited by 94 publications

References 78 publications

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status—A Pilot Study

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status—A Pilot Study

<p>Comparison of the Therapeutic Effect of Allogeneic and Xenogeneic Small Extracellular Vesicles in Soft Tissue Repair</p>

A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation

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