Evaluation of osteogenic induction potency of miR-27a-3p in adipose tissue-derived human mesenchymal stem cells (AD-hMSCs)

Arab, Fatemeh; Aghaee‐Bakhtiari, Seyed Hamid; Pasdar, Alireza; Saburi, Ehsan

doi:10.1007/s11033-022-08084-8

Cited by 5 publications

(4 citation statements)

References 66 publications

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“…Thus, in most experiments (Figs 2 – 5 and S2B ), the Colo320 cells were used. In addition, other mechanisms, such as neddylation [ 43 ], GSK3β mTOR-dependent phosphorylation [ 44 ], and microRNAs’ expression [ 45 ], that have been shown to be involved in regulating β-catenin levels may be influenced by the readthrough-inducing drugs and restrict the effects on β-catenin.…”

Section: Resultsmentioning

confidence: 99%

Nonsense mutation suppression is enhanced by targeting different stages of the protein synthesis process

Wittenstein,

Caspi,

Rippin

et al. 2023

PLoS Biol

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The introduction of premature termination codons (PTCs), as a result of splicing defects, insertions, deletions, or point mutations (also termed nonsense mutations), lead to numerous genetic diseases, ranging from rare neuro-metabolic disorders to relatively common inheritable cancer syndromes and muscular dystrophies. Over the years, a large number of studies have demonstrated that certain antibiotics and other synthetic molecules can act as PTC suppressors by inducing readthrough of nonsense mutations, thereby restoring the expression of full-length proteins. Unfortunately, most PTC readthrough-inducing agents are toxic, have limited effects, and cannot be used for therapeutic purposes. Thus, further efforts are required to improve the clinical outcome of nonsense mutation suppressors. Here, by focusing on enhancing readthrough of pathogenic nonsense mutations in the adenomatous polyposis coli (APC) tumor suppressor gene, we show that disturbing the protein translation initiation complex, as well as targeting other stages of the protein translation machinery, enhances both antibiotic and non-antibiotic-mediated readthrough of nonsense mutations. These findings strongly increase our understanding of the mechanisms involved in nonsense mutation readthrough and facilitate the development of novel therapeutic targets for nonsense suppression to restore protein expression from a large variety of disease-causing mutated transcripts.

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Section: Resultsmentioning

confidence: 99%

Nonsense mutation suppression is enhanced by targeting different stages of the protein synthesis process

Wittenstein,

Caspi,

Rippin

et al. 2023

PLoS Biol

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“…We found 51 differentially expressed miRNAs through microRNA sequencing. Among the upregulated 26 miRNAs, has-miR-483-3p [ 39 – 41 ], has-miR-486-5p [ 42 ], has-miR-22-3p [ 43 ], and has-miR-27a-3p [ 44 , 45 ] have been confirmed to promote osteogenesis; however, their effects on dentinogenesis remain to be examined. A series of studies have revealed that the promotion of odontoblast differentiation by EVs from dental mesenchymal stem cells may be achieved through regulating multiple signaling pathways (such as Wnt/β-catenin [ 32 ], p38/MAPK [ 13 ], and TGF-β/smads [ 15 ]) by microRNA, and proteins were carried by EVs.…”

Section: Discussionmentioning

confidence: 99%

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

Lu,

Mu,

et al. 2024

J Nanobiotechnol

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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.

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“…Modifications of adipose tissue stem cells are aimed, among others, at increasing the proliferative activity of cells, migration, and chemotaxis, increased production of active factors (cytokines, growth factors, exosomes) as well as more effective differentiation into other types of cells, especially osteocytes and chondrocytes [ 106 ]. For example, transfected AD-MSCs with miR-27a-3pAD-MSCs had a higher potential to differentiate into osteoblasts, which may be important in the therapy of bone damage and fractures [ 107 ]. AD-MSCs are also a good tool for genetic modification.…”

Section: Bioengineered Ad-mscs In Regenerative Medicinementioning

confidence: 99%

Adipose-Derived Mesenchymal Stromal Cells in Basic Research and Clinical Applications

Czerwiec

Zawrzykraj

Deptuła

et al. 2023

IJMS

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Adipose-derived mesenchymal stromal cells (AD-MSCs) have been extensively studied in recent years. Their attractiveness is due to the ease of obtaining clinical material (fat tissue, lipoaspirate) and the relatively large number of AD-MSCs present in adipose tissue. In addition, AD-MSCs possess a high regenerative potential and immunomodulatory activities. Therefore, AD-MSCs have great potential in stem cell-based therapies in wound healing as well as in orthopedic, cardiovascular, or autoimmune diseases. There are many ongoing clinical trials on AD-MSC and in many cases their effectiveness has been proven. In this article, we present current knowledge about AD-MSCs based on our experience and other authors. We also demonstrate the application of AD-MSCs in selected pre-clinical models and clinical studies. Adipose-derived stromal cells can also be the pillar of the next generation of stem cells that will be chemically or genetically modified. Despite much research on these cells, there are still important and interesting areas to explore.

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Evaluation of osteogenic induction potency of miR-27a-3p in adipose tissue-derived human mesenchymal stem cells (AD-hMSCs)

Cited by 5 publications

References 66 publications

Nonsense mutation suppression is enhanced by targeting different stages of the protein synthesis process

Nonsense mutation suppression is enhanced by targeting different stages of the protein synthesis process

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

Adipose-Derived Mesenchymal Stromal Cells in Basic Research and Clinical Applications

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