PF127 Hydrogel-Based Delivery of Exosomal CTNNB1 from Mesenchymal Stem Cells Induces Osteogenic Differentiation during the Repair of Alveolar Bone Defects

He, Longlong; Zhou, Qin; Zhang, Hengwei; Zhao, Ning; Liao, Lin

doi:10.3390/nano13061083

Cited by 11 publications

(3 citation statements)

References 52 publications

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“…JUN families include c-Jun is involved in the expression of various inflammatory genes by binding to their transcription factor binding sites. The c-Jun binds to the proximal IL-6 promoter and promotes IL-6 production which has been associated with accelerated osteoclastogenesis and elevated bone resorption (35). CTNNB1 encodes b-catenin which is a key player in the canonical Wnt/b-catenin signaling pathway (36), and has been shown regulate osteoblastic differentiation and osteoclastogenesis (37).…”

Section: Discussionmentioning

confidence: 99%

Decoding the mechanism of Eleutheroside E in treating osteoporosis via network pharmacological analysis and molecular docking of osteoclast-related genes and gut microbiota

Zhou,

et al. 2023

Front. Endocrinol.

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ObjectiveEleutheroside E (EE) is an anti-inflammatory natural compound derived from the edible medicinal herb Acanthopanax senticosus. This study aims to investigate the underlying mechanism of the anti-osteoporosis action of EE through network pharmacology, molecular docking and gut microbiota.Materials and methodsNetwork pharmacology was used to explore the potential core targets and main pathways mediated by EE in osteoporosis (OP) treatment. Molecular docking was exploited to investigate the interactions between the active anti-OP compounds in EE and the potential downstream targets. Following the multi-approach bioinformatics analysis, ovariectomy (OVX) model was also established to investigate the in vivo anti-OP effects of EE.ResultsThe top 10 core targets in PPI network were TP53, AKT1, JUN, CTNNB1, STAT3, HIF1A, EP300, CREB1, IL1B and ESR1. Molecular docking results that the binding energy of target proteins and the active compounds was approximately between −5.0 and −7.0 kcal/mol, which EE has the lowest docking binding energy with HIF1A. Enrichment analysis of GO and KEGG pathways of target proteins indicated that EE treatment could potentially alter numerous biological processes and cellular pathways. In vivo experiments demonstrated the protective effect of EE treatment against accelerated bone loss, where reduced serum levels of TRAP, CTX, TNF-α, LPS, and IL-6 and increased bone volume and serum levels of P1NP were observed in EE-treated mice. In addition, changes in gut microbiota were spotted by 16S rRNA gene sequencing, showing that EE treatment increased the relative abundance of Lactobacillus and decreased the relative abundance of Clostridiaceae.ConclusionIn summary, these findings suggested that the characteristics of multi-target and multi-pathway of EE against OP. In vivo, EE prevents the onset of OP by regulating gut microbiota and inflammatory response and is therefore a potential OP drug.

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Section: Discussionmentioning

confidence: 99%

Decoding the mechanism of Eleutheroside E in treating osteoporosis via network pharmacological analysis and molecular docking of osteoclast-related genes and gut microbiota

Zhou,

et al. 2023

Front. Endocrinol.

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“…This composite patch showed enhanced skin wound healing in rat model, a promising and effective strategy for clinical applications of therapeutic exosomes [30]. Recent studies supporting application of exosomes with electroconductive hydrogels highlight stable integration of exosome in nanofibrous structures without compromising hydrogel electrical activity and mechanical properties while maintaining therapeutic properties of the exosomes [63,64,95,96]. Nanofibers have been explored for isolation, delivery, biosensing, bioimaging, preservation and spatial analysis of exosome [37,[97][98][99].…”

Section: Electrospinning With Exosomesmentioning

confidence: 99%

Spinning with exosomes: electrospun nanofibers for efficient targeting of stem cell-derived exosomes in tissue regeneration

Raj,

Agrawal,

Bhutani

et al. 2024

Biomed. Mater.

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Electrospinning technique converts polymeric solutions into nanoscale fibers using an electric field and can be used for various biomedical and clinical applications. Extracellular vesicles (EVs) are cell-derived small lipid vesicles enriched with biological cargo (proteins and nucleic acids) potential therapeutic applications. In this review, we discuss extending the scope of electrospinning by incorporating stem cell-derived EVs, particularly exosomes, into nanofibers for their effective delivery to target tissues. The parameters used during the electrospinning of biopolymers limit the stability and functional properties of cellular products. However, with careful consideration of process requirements, these can significantly improve stability, leading to longevity, effectiveness, and sustained and localized release. Electrospun nanofibers are known to encapsulate or surface-adsorb biological payloads such as therapeutic EVs, proteins, enzymes, and nucleic acids. Small EVs, specifically exosomes, have recently attracted the attention of researchers working on regeneration and tissue engineering because of their broad distribution and enormous potential as therapeutic agents. This review focuses on current developments in nanofibers for delivering therapeutic cargo molecules, with a special emphasis on exosomes. It also suggests prospective approaches that can be adapted to safely combine these two nanoscale systems and exponentially enhance their benefits in tissue engineering, medical device coating, and drug delivery applications.

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“…Extensive research has been conducted using MSC therapies in both animal models and patients, employing different methods such as direct MSC injection, seeding MSCs on synthetic scaffolds, utilizing gene-modified MSCs, and employing allogenic MSC application. The literature surrounding the use of genetically modified MSCs as well as MSCs on synthetic scaffolds has shown positive results in terms of promoting osteogenic differentiation of MSCs and bone regrowth in both animal and human studies [87,88]. While there has been less research on non-scaffolded ASCs in bone regrowth, results from some studies have shown that the use of non-scaffolded MSCs can induce bone regrowth in patients with bone lesions or defects [89].…”

Section: Msc-based Strategies For Bone Regeneration In Vivomentioning

confidence: 99%

Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients

Baron,

Drohat,

Crawford

et al. 2023

Bioengineering

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Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone regeneration arise. To determine the appropriate amount of bone to be removed, preoperative imaging techniques such as bone and CT scans are employed. To prevent local recurrence, the current standard of care suggests maintaining bony and soft tissue margins from 3 to 7 cm beyond the tumor. The amount of bone removed in an OS patient leaves too large of a deficit for bone to form on its own and requires reconstruction with metal implants or allografts. Both methods require the bone to heal, either to the implant or across the allograft junction, often in the setting of marrow-killing chemotherapy. Therefore, the issue of bone regeneration within the surgically resected margins remains an important challenge for the patient, family, and treating providers. Mesenchymal stem/stromal cells (MSCs) are potential agents for enhancing bone regeneration post tumor resection. MSCs, used with scaffolds and growth factors, show promise in fostering bone regeneration in OS cases. We spotlight two MSC types—bone marrow-derived (BM-MSCs) and adipose tissue-derived (ASCs)—highlighting their bone regrowth facilitation and immunomodulatory effects on immune cells like macrophages and T cells, enhancing therapeutic outcomes. The objective of this review is two-fold: review work demonstrating any ability of MSCs to target the deranged immune system in the OS microenvironment, and synthesize the available literature on the use of MSCs as a therapeutic option for stimulating bone regrowth in OS patients post bone resection. When it comes to repairing bone defects, both MB-MSCs and ASCs hold great potential for stimulating bone regeneration. Research has showcased their effectiveness in reconstructing bone defects while maintaining a non-tumorigenic role following wide resection of bone tumors, underscoring their capability to enhance bone healing and regeneration following tumor excisions.

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PF127 Hydrogel-Based Delivery of Exosomal CTNNB1 from Mesenchymal Stem Cells Induces Osteogenic Differentiation during the Repair of Alveolar Bone Defects

Cited by 11 publications

References 52 publications

Decoding the mechanism of Eleutheroside E in treating osteoporosis via network pharmacological analysis and molecular docking of osteoclast-related genes and gut microbiota

Decoding the mechanism of Eleutheroside E in treating osteoporosis via network pharmacological analysis and molecular docking of osteoclast-related genes and gut microbiota

Spinning with exosomes: electrospun nanofibers for efficient targeting of stem cell-derived exosomes in tissue regeneration

Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients

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