دورية أكاديمية

Functional extracellular vesicles from SHEDs combined with gelatin methacryloyl promote the odontogenic differentiation of DPSCs for pulp regeneration.

التفاصيل البيبلوغرافية
العنوان: Functional extracellular vesicles from SHEDs combined with gelatin methacryloyl promote the odontogenic differentiation of DPSCs for pulp regeneration.
المؤلفون: Lu H; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China., Mu Q; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China., Ku W; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China., Zheng Y; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China., Yi P; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China., Lin L; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China., Li P; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China., Wang B; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China., Wu J; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China., Yu D; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China. yudsh@mail.sysu.edu.cn., Zhao W; Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China. zhaowei3@mail.sysu.edu.cn.
المصدر: Journal of nanobiotechnology [J Nanobiotechnology] 2024 May 17; Vol. 22 (1), pp. 265. Date of Electronic Publication: 2024 May 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, 2003-
مواضيع طبية MeSH: Dental Pulp*/cytology , Extracellular Vesicles*/chemistry , Gelatin*/chemistry , Gelatin*/pharmacology , Cell Differentiation*/drug effects , Odontogenesis*/drug effects , Stem Cells*/drug effects , Stem Cells*/cytology , Stem Cells*/metabolism , Regeneration*/drug effects , Tooth, Deciduous*/cytology , Methacrylates*/chemistry , Methacrylates*/pharmacology, Humans ; Animals ; Mice ; Cell Proliferation/drug effects ; Mice, Nude ; Cells, Cultured ; Hydrogels/chemistry ; Hydrogels/pharmacology ; Cell Movement/drug effects
مستخلص: Background: Pulp regeneration is a novel approach for the treatment of immature permanent teeth with pulp necrosis. This technique includes the combination of stem cells, scaffolds, and growth factors. Recently, stem cell-derived extracellular vesicles (EVs) have emerged as a new methodology for pulp regeneration. Emerging evidence has proven that preconditioning is an effective scheme to modify EVs for better therapeutic potency. Meanwhile, proper scaffolding is of great significance to protect EVs from rapid clearance and destruction. This investigation aims to fabricate an injectable hydrogel loaded with EVs from pre-differentiated stem cells from human exfoliated deciduous teeth (SHEDs) and examine their effects on pulp regeneration.
Results: We successfully employed the odontogenic induction medium (OM) of SHEDs to generate functional EV (OM-EV). The OM-EV at a concentration of 20 µg/mL was demonstrated to promote the proliferation and migration of dental pulp stem cells (DPSCs). The results revealed that OM-EV has a better potential to promote odontogenic differentiation of DPSCs than common EVs (CM-EV) in vitro through Alizarin red phalloidin, alkaline phosphatase staining, and assessment of the expression of odontogenic-related markers. High-throughput sequencing suggests that the superior effects of OM-EV may be attributed to activation of the AMPK/mTOR pathway. Simultaneously, we prepared a photocrosslinkable gelatin methacryloyl (GelMA) to construct an OM-EV-encapsulated hydrogel. The hydrogel exhibited sustained release of OM-EV and good biocompatibility for DPSCs. The released OM-EV from the hydrogel could be internalized by DPSCs, thereby enhancing their survival and migration. In tooth root slices that were subcutaneously transplanted in nude mice, the OM-EV-encapsulated hydrogel was found to facilitate dentinogenesis. After 8 weeks, there was more formation of mineralized tissue, as well as higher levels of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1).
Conclusions: The effects of EV can be substantially enhanced by preconditioning of SHEDs. The functional EVs from SHEDs combined with GelMA are capable of effectively promoting dentinogenesis through upregulating the odontogenic differentiation of DPSCs, which provides a promising therapeutic approach for pulp regeneration.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 81974146 National Natural Sciences Foundation of China; 2023A1515012554 Guangdong Natural Sciences Foundation; 2019015 Sun Yat-sen University Clinical Research 5010 Programme
فهرسة مساهمة: Keywords: Extracellular vesicles; Hydrogel; Odontogenic differentiation; Pulp regeneration; Stem cells from human exfoliated deciduous teeth
المشرفين على المادة: 0 (gelatin methacryloyl)
تواريخ الأحداث: Date Created: 20240517 Date Completed: 20240518 Latest Revision: 20240521
رمز التحديث: 20240521
مُعرف محوري في PubMed: PMC11102175
DOI: 10.1186/s12951-024-02542-0
PMID: 38760763
قاعدة البيانات: MEDLINE
الوصف
تدمد:1477-3155
DOI:10.1186/s12951-024-02542-0