1,721,028 research outputs found
Unraveling the Role of the Apical Papilla During Dental Root Maturation
No full textThe apical papilla is a stem cell rich tissue located at the base of the developing dental root and is responsible for the progressive elongation and maturation of the root. The multipotent stem cells of the apical papilla (SCAP) are extensively studied in cell culture since they demonstrate a high capacity for osteogenic, adipogenic, and chondrogenic differentiation and are thus an attractive stem cell source for stem cell-based therapies. Currently, only few studies are dedicated to determining the role of the apical papilla in dental root development. In this review, we will focus on the architecture of the apical papilla and describe the specific SCAP signaling pathways involved in root maturation. Furthermore, we will explore the heterogeneity of the SCAP phenotype within the tissue and determine their micro-environmental interaction. Understanding the mechanism of postnatal dental root growth could further aid in developing novel strategies in dental root regeneration.TV and PG were postdoctoral researchers, supported by the Research Foundation—Flanders (FWO—Vlaanderen; 12U7718N, 1502120N, 12Z2620N)
The Effect of Leukocyte- and Platelet-Rich Fibrin on Central and Peripheral Nervous System Neurons-Implications for Biomaterial Applicability
No full textLeukocyte- and Platelet-Rich Fibrin (L-PRF) is a second-generation platelet concentrate that is prepared directly from the patient's own blood. It is widely used in the field of regenerative medicine, and to better understand its clinical applicability we aimed to further explore the biological properties and effects of L-PRF on cells from the central and peripheral nervous system. To this end, L-PRF was prepared from healthy human donors, and confocal, transmission, and scanning electron microscopy as well as secretome analysis were performed on these clots. In addition, functional assays were completed to determine the effect of L-PRF on neural stem cells (NSCs), primary cortical neurons (pCNs), and peripheral dorsal root ganglion (DRG) neurons. We observed that L-PRF consists of a dense but porous fibrin network, containing leukocytes and aggregates of activated platelets that are distributed throughout the clot. Antibody array and ELISA confirmed that it is a reservoir for a plethora of growth factors. Key molecules that are known to have an effect on neuronal cell functions such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) were slowly released over time from the clots. Next, we found that the L-PRF secretome had no significant effect on the proliferative and metabolic activity of NSCs, but it did act as a chemoattractant and improved the migration of these CNS-derived stem cells. More importantly, L-PRF growth factors had a detrimental effect on the survival of pCNs, and consequently, also interfered with their neurite outgrowth. In contrast, we found a positive effect on peripheral DRG neurons, and L-PRF growth factors improved their survival and significantly stimulated the outgrowth and branching of their neurites. Taken together, our study demonstrates the positive effects of the L-PRF secretome on peripheral neurons and supports its use in regenerative medicine but care should be taken when using it for CNS applications
The Impact of Advanced Glycation End-Products (AGEs) on Proliferation and Apoptosis of Primary Stem Cells: A Systematic Review
No full textStem cell-based regenerative therapies hold great promises to treat a wide spectrum of diseases. However, stem cell engraftment and survival are still challenging due to an unfavorable transplantation environment. Advanced glycation end-products (AGEs) can contribute to the generation of these harmful conditions. AGEs are a heterogeneous group of glycated products, nonenzymatically formed when proteins and/or lipids become glycated and oxidized. Our typical Western diet as well as cigarettes contain high AGEs content. AGEs are also endogenously formed in our body and accumulate with senescence and in pathological situations. Whether AGEs have an impact on stem cell viability in regenerative medicine remains unclear, and research on the effect of AGEs on stem cell proliferation and apoptosis is still ongoing. Therefore, this systematic review provides a clear overview of the effects of glycated proteins on cell viability in various types of primary isolated stem cells used in regenerative medicine.Figures were created using images from Servier Medical Art Commons Attribution 3.0 Unported License (http://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License. This work was supported by a Bijzonder onderzoeksfonds (BOF) grant from Hasselt University (grant number: 16NI05BOF). HB benefits from an aspirant PhD mandate (grant number: 1154120N) of the `Research Foundation-Flanders' (fonds voor wetenschappelijk onderzoek (FWO)). PG is also supported by the FWO (grant numbers: 12U7718N and 1502120N).Bito, V (corresponding author), Hasselt Univ, Biomed BIOMED Res Inst, Agoralaan Bldg C, B-3590 Diepenbeek, Belgium.
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Phloretin enhances remyelination by stimulating OPC differentiation
No full textthe number of activated and quiescent NSCs, indicating that ET-1 signaling is required for maintenance of NSCs in the healthy adult mouse. Following focal demyelination of the corpus callosum, SVZ NSCs upregulated expression of ET-1. Ablation of ET-1 reduced the percentages of proliferating NSCs and proliferating OPCs in the SVZ, suggesting that ET-1 plays a critical role in the SVZ proliferative response to injury. RNAseq of cultured primary NSCs and OPCs treated with ET-1 identified genes involved in stem cell maintenance, including Notch signaling, and OPC migration. Lastly, we confirmed that ET-1 and EDNRB expression are conserved in the adult human SVZ, indicating that this pathway may be a potential target for promoting SVZ-mediated cellular repair. Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Why endogenous repair mechanisms frequency fail in these disorders is poorly understood, however, there is now strong evidence that this is related to an overly inflammatory microenvironment combined with the intrinsic inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature myelinating cells. Previously, we found that phloretin, a flavonoid abundantly present in apples and strawberries reduces neuroinflammation by driving macrophages towards an anti-inflammatory phenotype. Here, we show that phloretin also markedly stimulates remyelination in ex vivo and in vivo animals models. However, improved remyelination was attributed to a direct impact of phloretin on OPC maturation and occurred autonomously from alterations in microglia function and inflammation. Mechanistically, phloretin activated the fatty acid sensing nuclear receptor peroxisome proliferator-activated receptor gamma PPARy, thereby promoting the maturation of OPC. Altogether, our findings indicate that phloretin has pro-regenerative properties in CNS disorders, with potentially broad implications for the development of therapeutic strategies and dietary interventions
EXPLORING THE ROLE OF PERIPHERAL MYELIN PROTEIN 22 EXPRESSION IN ORDERED MEMBRANE DOMAINS OF SCHWANN CELL DIFFERENTIATED DENTAL PULP STEM CELLS AND HOW IT AFFECTS CELL-MATRIX INTERACTIONS
No full textNew therapeutic strategies to establish repair of injured peripheral nerves are desperately needed. For this purpose, our group developed Engineered Neural Tissue with Schwann cell differentiated human dental pulp stem cells (SC-hDPSC) embedded in an aligned collagen hydrogel 1, 2. The use of SC-DPSCs as a cell source for nerve repair has several advantages but there is a need to better understand how they interact with the extracellular matrix (ECM) and how this affects their myelinating behavior. We aim to investigate the role of peripheral myelin protein 22 (PMP22) in the interaction of SC-hDPSCs with an endoneurial-like ECM. SC-hDPSC were cultured on 2D coated surfaces and by performing immunostainings combined with confocal-and super resolution STORM microscopy we showed that PMP22 is expressed in lipid rafts of the plasma membrane. Live cell/TIRF imaging experiments with cholera toxin b showed that these lipid rafts are highly dynamic. We also observed a strong colocalization between PMP22 and integrin b1, a6, and b4 in the membrane of SC-hDPSC. In addition, SC DPSC cultured in aligned or free floating hydrogels strongly interact with collagen I fibres via these integrins, which was confirmed macro-scopically and with label-free second harmonic generation microscopy. In conclusion, we showed that PMP22 is expressed in ordered regions in the SC-hDPSC membrane together with integrins that are important for cell interactions with the ECM and in myelination. This implicates that PMP22 may play a role in controlling myelination, but this will be explored in future experiments
EXPLORING THE ROLE OF PERIPHERAL MYELIN PROTEIN 22 EXPRESSION IN ORDERED MEMBRANE DOMAINS OF SCHWANN CELL DIFFERENTIATED DENTAL PULP STEM CELLS AND HOW IT AFFECTS CELL-MATRIX INTERACTIONS
No full textNew therapeutic strategies to establish repair of injured peripheral nerves are desperately needed. For this purpose, our group developed Engineered Neural Tissue with Schwann cell differentiated human dental pulp stem cells (SC-hDPSC) embedded in an aligned collagen hydrogel 1, 2. The use of SC-DPSCs as a cell source for nerve repair has several advantages but there is a need to better understand how they interact with the extracellular matrix (ECM) and how this affects their myelinating behavior. We aim to investigate the role of peripheral myelin protein 22 (PMP22) in the interaction of SC-hDPSCs with an endoneurial-like ECM. SC-hDPSC were cultured on 2D coated surfaces and by performing immunostainings combined with confocal-and super resolution STORM microscopy we showed that PMP22 is expressed in lipid rafts of the plasma membrane. Live cell/TIRF imaging experiments with cholera toxin b showed that these lipid rafts are highly dynamic. We also observed a strong colocalization between PMP22 and integrin b1, a6, and b4 in the membrane of SC-hDPSC. In addition, SC DPSC cultured in aligned or free floating hydrogels strongly interact with collagen I fibres via these integrins, which was confirmed macro-scopically and with label-free second harmonic generation microscopy. In conclusion, we showed that PMP22 is expressed in ordered regions in the SC-hDPSC membrane together with integrins that are important for cell interactions with the ECM and in myelination. This implicates that PMP22 may play a role in controlling myelination, but this will be explored in future experiments
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Targeting lipophagy in macrophages improves repair in multiple sclerosis
No full textFoamy macrophages containing abundant intracellular myelin remnants are an important pathological hallmark of multiple sclerosis. Reducing the intracellular lipid burden in foamy macrophages is considered a promising therapeutic strategy to induce a phagocyte phenotype that promotes central nervous system repair. Recent research from our group showed that sustained intracellular accumulation of myelin-derived lipids skews these phagocytes toward a disease-promoting and more inflammatory phenotype. Our data now demonstrate that disturbed lipophagy, a selective form of autophagy that helps with the degradation of lipid droplets, contributes to the induction of this phenotype. Stimulating autophagy using the natural disaccharide trehalose reduced the lipid load and inflammatory phenotype of myelin-laden macrophages. Importantly, trehalose was able to boost remyelination in the ex vivo brain slice model and the in vivo cuprizone-induced demyelination model. In summary, our results provide a molecular rationale for impaired metabolism of myelin-derived lipids in macrophages, and identify lipophagy induction as a promising treatment strategy to promote remyelination.The work has been supported by the Flemish Fund for ScientificResearch (FWO Vlaanderen; 1141920N, 12U7718N and 1502120N), theBelgian Charcot Foundation (Fondation Charcot 2020-0004), and thespecial research fund UHasselt (BOF
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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