Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis

Lee, Yeon-Hee; Park, Heekyung; Auh, Q‐Schick; Nah, Haram; Lee, Jae Seo; Moon, Hojin; Heo, Dong Nyoung; Kim, In San; Kwon, Il Keun

doi:10.3390/ijms21041541

Cited by 71 publications

(79 citation statements)

References 98 publications

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“…The biological function of stem cells is mainly achieved by stimulating effector cells with specific biologically active molecules carried in the exocrine body. Studies have shown that BMSC-Exos can promote bone regeneration by promoting osteogenesis and angiogenesis (Nakamura et al, 2015;Xue et al, 2018;Takeuchi et al, 2019;Lee et al, 2020;Xu et al, 2020;Zhang L. et al, 2020). Therefore, our study aimed to investigate the effect of BMSC-Exos-HIF1α on the proliferation and osteogenic differentiation of BMSCs, investigating the biological function of BMSC-Exos-HIF1α loading on β-TCP scaffold material to repair bone defects in rats.…”

Section: Discussionmentioning

confidence: 99%

BMSC-Exosomes Carry Mutant HIF-1α for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects

Ying

Wang

et al. 2020

Front. Bioeng. Biotechnol.

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Repair and reconstruction of critical-sized bone defects has always been a difficult task in orthopedics. Hypoxia inducible factor-1α (HIF-1α) plays an important role in bone defect repair, it has the dual function of promoting osteogenesis and vascular regeneration, but it is quickly degraded by the body under normoxic conditions. Previously we prepared mutant HIF-1α, which has been shown to efficiently maintain cellular expression under normoxic conditions. In this study, we evaluated for the first time the role of exosomes of rat bone marrow mesenchymal stem cell carry mutant HIF-1α (BMSC-Exos-HIF1α) in repairing critical-sized bone defects. Evaluation of the effects of BMSC-Exos-HIF1α on bone marrow mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation by cell proliferation assay, alkaline phosphatase activity assay, alizarin red staining, real-time quantitative polymerase chain reaction. BMSC-Exos-HIF1α was loaded onto the β-TCP stent implanted in the bone defect area using a rat cranial critical-sized bone defect model, and new bone formation and neovascularization were detected in vivo by micro-CT, fluorescence labeling analysis, Microfil perfusion, histology and immunohistochemical analysis. In vitro results showed that BMSC-Exos-HIF1α stimulated the proliferation of BMSCs and upregulated the expression level of bone-related genes, which was superior to bone marrow MSC exosomes (BMSC-Exos). In vivo results showed that BMSC-Exos-HIF1α combined with β-TCP scaffold promoted new bone regeneration and neovascularization in the bone defect area, and the effect was better than that of BMSC-Exos combined with β-TCP scaffold. In this study, the results showed that BMSC-Exos-HIF1α stimulated the proliferation and osteogenic differentiation of BMSCs and that BMSC-Exos-HIF1α combined with β-TCP scaffolds could repair critical-sized bone defects by promoting new bone regeneration and neovascularization.

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Section: Discussionmentioning

confidence: 99%

BMSC-Exosomes Carry Mutant HIF-1α for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects

Ying

Wang

et al. 2020

Front. Bioeng. Biotechnol.

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“…Overall, a shift of transcriptional resources of immune cells in individuals with TMD to a proinflammatory state may contribute to somatic symptoms (pain and fatigue), although it is also possible that chronic pain causes SNS activation (through stressful experience). In addition to limiting healing of damaged tissue of the temporomandibular joint and muscle, 26 this shift to a proinflammatory state of peripheral immune cells in individuals with TMD may result in a direct 45 , 48 and/or indirect (eg, synovial fluid of the temporomandibular joint 25 ) enhancement of neuronal sensory processing. Preclinical evidence suggests that elevated levels of peripheral inflammation lead to activation of glial cells in peripheral (eg, trigeminal ganglia) and central nervous systems, 46 which can increase release of inflammatory mediators and amplify neuronal excitability, which in turn leads to an increased hypersensitivity to painful stimuli within these neuronal structures.…”

Section: Resultsmentioning

confidence: 99%

Preliminary evidence for conserved transcriptional response to adversity in adults with temporomandibular disorder

King¹,

Boggero²,

Schulert³

et al. 2021

PR9

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Introduction: Temporomandibular disorder (TMD) is one of the most common orofacial pain conditions. Alteration in immune functioning is one promising biological mechanism underlying pain in TMD. However, there is a gap in the understanding of molecular bases contributing to altered immune functioning in these patients. Objectives: In the current study, we investigated whether individuals with TMD would exhibit differential activity of 3 specific transcription factors involved in inflammatory (nuclear factor-kappa B, NF-kB), antiviral (interferon-regulatory factors, IRF), and sympathetic (cAMP response element-binding protein, CREB) processes using a promoter-based bioinformatics analysis, which is characterized as the “Conserved Transcriptional Response to Adversity.” Methods: Adults with TMD (n = 19) and without (n = 17) underwent a standardized clinical examination for TMD. A blood sample was collected for genome-wide transcriptional RNA profiling. Bioinformatic analyses tested for differential prevalence of proinflammatory and antiviral transcription factor activity in core promoter sequences from all genes showing >1.2-fold differential expression in TMD vs controls. Results: Promoter-based bioinformatic analyses of genome-wide transcriptome profiles confirmed upregulation of genes bearing response elements for proinflammatory transcription factor (NF-kB, P = 0.002) and downregulation of genes with response elements for IRF (P = 0.037) in patients with TMD relative to controls. Results also indicated upregulated activity of CREB in patients with TMD (P = 0.08), consistent with increased activity of the sympathetic nervous system. Conclusion: These results provide initial support that the regulation of immune pathways is altered in individuals with TMD. A shift of transcriptional resources to a proinflammatory state may be driven by psychosocial stress and contributes to symptoms associated with TMD.

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“…In addition, exosomes are a cell-free treatment option that are nonimmunogenic in nature, possess an intrinsic ability to be selectively delivered to target tissues and have long circulation times in the body, making them ideal candidates for targeted therapy by effectively transferring different types of molecules upon genetic modi cation [30][31][32]. Biological modi cation with pro-regenerative factors may enhance the innate therapeutic capability of exosomes [33]. In addition, due to their native structure and characteristics, exosomes function as promising slow-release reservoirs of molecules inside the body, providing a steady stream of the therapeutic molecules [18,30,34].…”

Section: Discussionmentioning

confidence: 99%

Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis

Cao

Yan

Chen

et al. 2020

Preprint

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Background: Spinal cord injury is a devastating clinical condition for which there are currently no effective therapeutic options. In the present study, we aim to investigate the effect of an administered injection of exosomes derived human urine stem cell (USC-Exo) embedded in hydrogel could improve the spinal cord functional recovery after injury and the underlying mechanism.Methods: Exosome were isolate from USC and identified by transmission electron Microscopy (TEM) and western blot. Functional assays in vitro were performed to assess the effects of USC-Exo on tube formation and migration, as well as their regulatory role in the PI3K/AKT signaling pathway activation. A locally administered injection of exosome embedded in hydrogel was used for SCI treatment. The effects of USC-Exo on functional recovery and the role of the candidate protein ANGPTL3 harboring in USC-Exo for promoting angiogenesis in SCI model was assessed.Results: In the current study, we demonstrate that a locally administered injection of USC-Exo embedded in hydrogel can pass the spinal cord blood brain barrier and deliver ANGPTL3 to the injured spinal cord region. In addition, the administration of human USC-Exo could enhance spinal cord neurological functional recovery by promoting angiogenesis. The results of mechanistic studies revealed that ANGPTL3 is enriched in (USC-Exo) and is required for their ability to promote angiogenesis. Functional studies further confirmed that the effects of USC-Exo on angiogenesis are mediated by the PI3K/AKT signaling pathway. Conclusion: Collectively, our results indicate that USC-Exo serve as a crucial regulator of angiogenesis by delivering ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

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Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis

Cited by 71 publications

References 98 publications

BMSC-Exosomes Carry Mutant HIF-1α for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects

BMSC-Exosomes Carry Mutant HIF-1α for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects

Preliminary evidence for conserved transcriptional response to adversity in adults with temporomandibular disorder

Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis

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