Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis

Tian, Jun; Chen, Weiyang; Xiong, Yingen; Li, Qianer; Kong, Siyi; Li, Mengjie; Pang, Chunfeng; Yu, Qin; Xu, Zhezhen; Gong, Qimei; Wang, Xi

doi:10.1016/j.bioactmat.2022.10.001

Cited by 30 publications

(26 citation statements)

References 73 publications

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“…Notably, approximately half of these miRNAs have previously been identified in EVs from bone marrow, adipose tissue, or umbilical cord MSCs, suggesting a common miRNA cargo in EVs from MSCs (53,59,60). Among these miRNAs, we observed the presence miR-210, miR-223-3p and let-7c-5p, which are noted for their ability to induce polarization towards an M2 phenotype in macrophages (61,62). Also of interest was the presence of miR-451a, which showed the highest expression.…”

Section: Discussionmentioning

confidence: 67%

Extracellular vesicles from dental pulp mesenchymal stem cells modulate macrophage phenotype during acute and chronic cardiac inflammation in athymic nude rats with myocardial infarction

Amaro-Prellezo,

Gómez-Ferrer,

Hakobyan

et al. 2024

Preprint

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Background/aims: Extracellular vesicles (EVs) derived from dental pulp mesenchymal stem cells (DP-MSCs) are a promising therapeutic option for the treatment of myocardial ischemia. The aim of this study was to determine whether MSC-EVs could promote a pro-resolving environment in the heart by modulating macrophage populations. Methods: EVs derived from three independent biopsies of DP-MSCs (MSC-EVs) were isolated by tangential flow-filtration and size exclusion chromatography, and were characterized by omics analyses. Biological processes associated with these molecules were analyzed using String and GeneCodis platforms. The immunomodulatory capacity of MSC-EVs to polarize macrophages towards a pro-resolving or M2-like phenotype was assessed by evaluating surface markers, cytokine production, and efferocytosis. The therapeutic potential of MSC-EVs was evaluated in an acute myocardial infarction (AMI) model in nude rats. Infarct size and the distribution of macrophage populations in the infarct area were evaluated 7 and 21 days after intramyocardial injection of MSC-EVs. Results: Lipidomic, proteomic, and miRNA-seq analysis of MSC-EVs revealed their association with biological processes involved in tissue regeneration and regulation of the immune system, among others. MSC-EVs promoted the differentiation of pro-inflammatory macrophages towards a pro-resolving phenotype, as evidenced by increased expression of M2 markers and decreased secretion of pro-inflammatory cytokines. Administration of MSC-EVs in rats with AMI limited the extent of the infarcted area at 7 and 21 days post-infarction. MSC-EV treatment also reduced the number of pro-inflammatory macrophages within the infarct area, promoting the resolution of inflammation. Conclusion: EVs derived from DP-MSCs exhibited similar characteristics at the omics level irrespective of the biopsy from which they were derived. All MSC-EVs exerted effective pro-resolving responses in a rat model of AMI, indicating their potential as therapeutic agents for the treatment of inflammation associated with AMI.

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Section: Discussionmentioning

confidence: 67%

Extracellular vesicles from dental pulp mesenchymal stem cells modulate macrophage phenotype during acute and chronic cardiac inflammation in athymic nude rats with myocardial infarction

Amaro-Prellezo,

Gómez-Ferrer,

Hakobyan

et al. 2024

Preprint

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“…The pathogenesis of SS involves the polarization of macrophages into the pro-inflammatory M1 phenotype [ 20 ], whereas EVs from tissue-derived MSCs reprogram macrophages into the anti-inflammatory M2 phenotype in mouse models of several inflammation-related diseases [ 21 , 22 ]. Since the spleen is essential for the pathogenesis of SS [ 18 ] and the primary target organ of IV infused iEVs, we examined the polarization of splenic macrophages from NOD.B10.H2 b mice at 2 weeks after last iEV treatment with flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

Inhibitory Effects of Extracellular Vesicles from iPS-Cell-Derived Mesenchymal Stem Cells on the Onset of Sialadenitis in Sjögren’s Syndrome Are Mediated by Immunomodulatory Splenocytes and Improved by Inhibiting miR-125b

Zhao

Bae

Shahsavari

et al. 2023

IJMS

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Extracellular vesicles (EVs) from allogeneic-tissue-derived mesenchymal stem cells (MSCs) are promising to improve Sjögren’s syndrome (SS) treatment, but their application is hindered by high variations in and limited expandability of tissue MSCs. We derived standardized and scalable MSCs from iPS cells (iMSCs) and reported that EVs from young but not aging iMSCs (iEVs) inhibited sialadenitis onset in SS mouse models. Here, we aim to determine cellular mechanisms and optimization approaches of SS-inhibitory effects of iEVs. In NOD.B10.H2b mice at the pre-disease stage of SS, we examined the biodistribution and recipient cells of iEVs with imaging, flow cytometry, and qRT-PCR. Intravenously infused iEVs accumulated in the spleen but not salivary glands or cervical lymph nodes and were mainly taken up by macrophages. In the spleen, young but not aging iEVs increased M2 macrophages, decreased Th17 cells, and changed expression of related immunomodulatory molecules. Loading miR-125b inhibitors into aging iEVs significantly improved their effects on repressing sialadenitis onset and regulating immunomodulatory splenocytes. These data indicated that young but not aging iEVs suppress SS onset by regulating immunomodulatory splenocytes, and inhibiting miR-125b in aging iEVs restores such effects, which is promising to maximize production of effective iEVs from highly expanded iMSCs for future clinical application.

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“…Mesenchymal stem cells derived from dental pulp are easily accessible, as they can be extracted from deciduous teeth naturally lost by children or third molars commonly indicated for extraction [ 88 ]. These cells have excellent differentiation potential and can be used to treat various tissues, including bones and cartilage [ 89 ].…”

Section: Discussionmentioning

confidence: 99%

Global Trends and Future Research Directions for Temporomandibular Disorders and Stem Cells

Silva

Melo

Ferreira

et al. 2023

JFB

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Temporomandibular disorder (TMD) is an umbrella term used to describe various conditions that affect temporomandibular joints, masticatory muscles, and associated structures. Although the most conservative and least invasive treatment is preferable, more invasive therapies should be employed to refractory patients. Tissue engineering has been presented as a promising therapy. Our study aimed to investigate trends and point out future research directions on TMD and stem cells. A comprehensive search was carried out in the Web of Science Core Collection (WoS-CC) in October 2022. The bibliometric parameters were analyzed through descriptive statistics and graphical mapping. Thus, 125 papers, published between 1992 and 2022 in 65 journals, were selected. The period with the highest number of publications and citations was between 2012 and 2022. China has produced the most publications on the subject. The most frequently used keywords were “cartilage”, “temporomandibular joint”, “mesenchymal stem cells”, and “osteoarthritis”. Moreover, the primary type of study was in vivo. It was noticed that using stem cells to improve temporomandibular joint repair and regeneration is a significant subject of investigation. Nonetheless, a greater understanding of the biological interaction and the benefits of using these cells in patients with TMD is required.

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Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis

Cited by 30 publications

References 73 publications

Extracellular vesicles from dental pulp mesenchymal stem cells modulate macrophage phenotype during acute and chronic cardiac inflammation in athymic nude rats with myocardial infarction

Extracellular vesicles from dental pulp mesenchymal stem cells modulate macrophage phenotype during acute and chronic cardiac inflammation in athymic nude rats with myocardial infarction

Inhibitory Effects of Extracellular Vesicles from iPS-Cell-Derived Mesenchymal Stem Cells on the Onset of Sialadenitis in Sjögren’s Syndrome Are Mediated by Immunomodulatory Splenocytes and Improved by Inhibiting miR-125b

Global Trends and Future Research Directions for Temporomandibular Disorders and Stem Cells

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