It was aim to study the physicochemical features and biocompatibility of electrospun collagen-chitosan membranes, and its potential in guided bone regeneration. Electrospinning technology was applied ...in the fabrication of electrospun collagen membranes and electrospun collagen-chitosan membranes following observation of scanning electron microscope. Physicochemical properties including tensile strength, elongation rate, porosity, degradation rate, and biocompatibility of membranes were measured then. In vivo, calvarial bone defects created on rats were covered with two kinds of membranes respectively. In the 4th and 8th week, enzyme-linked immunosorbent assay testing bone alkaline phosphatase and osteocalcin, Micro CT analyzing bone volume, bone volume/total volume, trabecular number and trabecular spacing values, and histological staining were carried out for evaluating the potentials of the membranes on bone regeneration. We found that regular and highly-porous structure favoring the adhesion and proliferation of periodontal ligament cells was observed in all electrospinning groups. Compared with electrospun collagen membranes, electrospun collagen-chitosan membranes performed better physiochemical features including higher tensile strength and more stable degradation rate. In the animal model, compared with the other groups, higher levels of bone alkaline phosphatase in the 4th week and osteocalcin in the 8th week were observed in the electrospun collagen-chitosan membrane. Meanwhile, both of the radiographical and histological results further confirmed that the new bone formation (with higher bone volume, bone volume/total volume, Trabecular number, and lower Trabecular spacing) were more active in the electrospun collagen-chitosan membrane. In conclusion, Electrospun collagen-chitosan membranes perform excellent physicochemical properties, biocompatibility, and great effects on guided bone regeneration, which as the membrane has good application prospect in tissue regeneration.
Deep caries, trauma, and severe periodontitis result in pulpitis, pulp necrosis, and eventually pulp loss. However, no clinical therapy can regenerate lost pulp. A novel pulp regeneration strategy ...for clinical application is urgently needed. Signaling transduction plays an essential role in regulating the regenerative potentials of dental stem cells. Cytokines or growth factors, such as stromal cell-derived factor (SDF), fibroblast growth factor (FGF), bone morphogenetic protein (BMP), vascular endothelial growth factor (VEGF), WNT, can promote the migration, proliferation, odontogenic differentiation, pro-angiogenesis, and pro-neurogenesis potentials of dental stem cells respectively. Using the methods of signaling modulation including growth factors delivery, genetic modification, and physical stimulation has been applied in multiple preclinical studies of pulp regeneration based on cell transplantation or cell homing. Transplanting dental stem cells and growth factors encapsulated into scaffold regenerated vascularized pulp-like tissue in the root canal. Also, injecting a flowable scaffold only with chemokines recruited endogenous stem/progenitor cells for pulp regeneration. Notably, dental pulp regeneration has gradually developed into the clinical phase. These findings enlightened us on a novel strategy for structural and functional pulp regeneration through elaborate modulation of signaling transduction spatially and temporally via clinically applicable growth factors delivery. But challenges, such as the adverse effects of unphysiological signaling activation, the controlled drug release system, and the safety of gene modulation, are necessary to be tested in future works for promoting the clinical translation of pulp regeneration.
The interaction between astrocytes and microglia plays a vital role in the damage and repair of brain lesions due to traumatic brain injury (TBI). Recent studies have shown that exosomes act as ...potent mediators involved in intercellular communication.
In the current study, the expression of inflammatory factors and miR-873a-5p in the lesion area and oedema area was evaluated in 15 patients with traumatic brain injury. Exosomes secreted by astrocytes were detected by immunofluorescence, Western blot and electron microscopy. A mouse model of TBI and an in vitro model of LPS-induced primary microglia were established to study the protective mechanism of exosomes from miR-873a-5p overexpressing in TBI-induced nerve injury.
We discovered that exosomes derived from activated astrocytes promote microglial M2 phenotype transformation following TBI. More than 100 miRNAs were detected in these astrocyte-derived exosomes. miR-873a-5p is a major component that was highly expressed in human traumatic brain tissue. Moreover, miR-873a-5p significantly inhibited LPS-induced microglial M1 phenotype transformation and the subsequent inflammation through decreased phosphorylation of ERK and NF-κB p65. This effect also greatly improved the modified neurological severity score (mNSS) and attenuated brain injury in a strictly controlled cortical impact mouse model.
Taken together, our research indicates that miRNAs in the exosomes derived from activated astrocytes play a key role in the astrocyte-microglia interaction. miR-873a-5p, as one of the main components of these astrocyte-derived exosomes, attenuated microglia-mediated neuroinflammation and improved neurological deficits following TBI by inhibiting the NF-κB signalling pathway. These findings suggest a potential role for miR-873a-5p in treating traumatic brain injury.
Adipose tissue is an active endocrine organ that can secrete a wide number of factors to regulate adipogenesis via paracrine signals. In addition to soluble proteins in adipose tissue, microRNAs ...(miRNAs) enriched in extracellular vesicles (EVs), such as exosomes or microvesicles, could modulate intercellular communications. In this study, we demonstrated that exosome-like vesicles derived from adipose tissue (Exo-AT) were internalized by adipose tissue-derived stem cells (ADSCs), and that these, in turn, induced adipogenesis. High-throughput sequencing showed that 45 miRNAs were enriched in Exo-AT, and 31.11% of them were associated with adipogenesis, compared with ADSC-derived exosome-like vesicles (Exo-ADSC). miR-450a-5p, one of the most abundant miRNAs in Exo-AT, was a proadipogenic miRNA. Further study demonstrated that miR-450a-5p promoted adipogenesis through repressing expression of WISP2 by targeting its 3' untranslated region. Additionally, Exo-AT could also downregulate the expression of WISP2, while miR-450a-5p inhibitor reversed this effect. Moreover, inhibition of miR-450a-5p impaired adipogenesis mediated by exosome-like vesicles. In conclusion, Exo-AT mediates adipogenic differentiation through a mechanism involving transfer of miR-450a-5p.
Nerous system diseases, both central and peripheral, bring an incredible burden onto patients and enormously reduce their quality of life. Currently, there are still no effective treatments to repair ...nerve lesions that do not have side effects. Stem cell–based therapies, especially those using dental stem cells, bring new hope to neural diseases. Dental stem cells, derived from the neural crest, have many characteristics that are similar to neural cells, indicating that they can be an ideal source of cells for neural regeneration and repair. This review summarizes the neural traits of all the dental cell types, including DPSCs, PDLCs, DFCs, APSCs and their potential applications in nervous system diseases. We have summed up the advantages of dental stem cells in neural repair, such as their neurotrophic and neuroprotective traits, easy harvest and low rejective reaction rate, among others. Taken together, dental stem cells are an ideal cell source for neural tissue regeneration and repair.
Apoptosis is a universal and continuous event during tissue development, restoration, repair, and regeneration. Mounting evidence has demonstrated that apoptosis is essential for the activation of ...tissue regeneration. However, the underlying mechanism remains elusive. A striking development in recent years comes from research on extracellular vesicles (EVs) derived from apoptotic cells. During apoptosis, cells secrete vesicles of various sizes containing various components. Apoptotic cell-derived EVs (ApoEVs) have been found to transit to neighboring cells or cells in distant tissues through the circulation. These vesicles could act as containers to transmit the nucleic acid, protein, and lipid signals to target cells. ApoEVs have been shown to promote regeneration in the cardiovascular system, skin, bone, muscle, kidney, etc. Moreover, several specific signaling pathways mediating the anabolic effects of ApoEVs have been classified. In this review, we comprehensively discussed the latest findings on the function of ApoEVs in tissue regeneration and disease prevention. These findings may reveal unexpected clues regarding the regulatory network between cell death and tissue regeneration and suggest novel targets for regenerative medicine. The findings discussed here also raise the question whether and to what extent ApoEVs contribute to embryonic development. This question is all the more urgent because the exact functions of apoptotic events during numerous developmental processes are still largely unclear.
Emerging studies of bioactive lipids have made many exciting discoveries in recent years. Sphingolipids and their metabolites perform a wide variety of cellular functions beyond energy metabolism. ...Emerging evidence based on genetically manipulated mouse models and molecular biology allows us to obtain new insights into the role sphingolipid played on skeletal remodeling. This review summarizes studies or understandings of the crosstalk between sphingomyelin, ceramide, and sphingosine-1-phosphate (S1P) of sphingolipids family and the cells, especially osteoblasts and osteoclasts of the bone through which bone is remodeled during life constantly. This review also shows agonists and antagonists of S1P as possible therapeutic options and opportunities on bone diseases.
Adipose-derived mesenchymal stem cells (ADSCs) are considered to be seed cells in bone tissue engineering and emerging evidence indicates that circular RNAs (circRNAs) function in the osteogenic ...differentiation of ADSCs. The mechanisms of osteoblastic differentiation of ADSCs from the perspective of circRNA modulation are examined in this study. First, circRNA-23525 was upregulated during osteoblastic differentiation of ADSCs. Second, overexpression of circRNA-23525 increased Runx2, ALP and OCN at both mRNA and protein levels. Alkaline phosphatase (ALP) and Alizarin Red staining indicated a similar tendency. Silencing circRNA-23525 produced the opposite effect. Bioinformatics analysis with luciferase assays confirmed that circRNA-23525 functioned as a sponge for miR-30a-3p. In the osteoblastic differentiation of ADSCs, the dynamic expression of miR-30a-3p and circRNA-23525 resulted in an opposite trend at 3, 7 and 14 days. Overexpression of circRNA-23525 downregulated miR-30a-3p and knockdown of circRNA-23525 promoted the expression of miR-30a-3p. Bioinformatics methods and luciferase assays suggested that miR-30a-3p modulated Runx2 expression by targeting 3′UTR. Knockdown of miR-30a-3p facilitated osteogenesis in ADSCs and enhancing miR-30a-3p interfered with the osteogenic process. Finally, circRNA-23525 overexpression significantly increased Runx2 expression, while co-transfection of miR-30a-3p mimics reversed it. Runx2 expression was decreased in circRNA-23525-knockdown ADSCs but expression was rescued by including the miR-30a-3p inhibitor in the osteoblastic process. ALP activity and mineralized bone matrix confirmed the function of circRNA-23525/miR-30a-3p in osteogenesis. Taken together, the current study demonstrated that circRNA-23525 regulates Runx2 expression via targeting miR-30a-3p and is thus a positive regulator in the osteoblastic differentiation of ADSCs.
The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The ...exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering.
Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored.
The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth.
Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.
Craniofacial tissue defects caused by trauma, developmental malformation, or surgery are critical issues of high incidence, which are harmful to physical and psychological health. Transplantation of ...engineered tissues or biomaterials is a potential method to repair defects and regenerate the craniofacial tissues. Revascularization is essential to ensure the survival and regeneration of the grafts. Since microvessels play a critical role in blood circulation and substance exchange, the pre-establishment of the microvascular network in transplants provides a technical basis for the successful regeneration of the tissue defect. In this study, we reviewed the recent development of strategies and applications of prevascularization in tissue engineering and regeneration of craniofacial tissues. We focused on the cellular foundation of the
prevascularized microvascular network, the cell source for prevascularization, and the strategies of prevascularization. Several key strategies, including coculture, microspheres, three-dimensional printing and microfluidics, and microscale technology, were summarized and the feasibility of these technologies in the clinical repair of craniofacial defects was discussed. Impact statement Prevascularization is an effective strategy to promote the survival and regeneration of the graft after transplantation. This review focuses on recent development in the technique of prevascularization and discusses the advantages and limits of current technologies. Furthermore, we summarized the progress in the repair of craniofacial tissue defect with prevascularization strategies. The development raised promising prospects of prevascularization strategies in the regeneration of cranial facial tissue defects in the future.
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