33 results on '"Vangansewinkel, Tim"'
Search Results
2. Proteostasis plays an important role in demyelinating Charcot Marie Tooth disease
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Libberecht, Karen, Vangansewinkel, Tim, Van Den Bosch, Ludo, Lambrichts, Ivo, and Wolfs, Esther
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- 2023
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3. PMP22 duplication dysregulates lipid homeostasis and plasma membrane organization in developing human Schwann cells.
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Prior, Robert, Silva, Alessio, Vangansewinkel, Tim, Idkowiak, Jakub, Tharkeshwar, Arun Kumar, Hellings, Tom P, Michailidou, Iliana, Vreijling, Jeroen, Loos, Maarten, Koopmans, Bastijn, Vlek, Nina, Agaser, Cedrick, Kuipers, Thomas B, Michiels, Christine, Rossaert, Elisabeth, Verschoren, Stijn, Vermeire, Wendy, Laat, Vincent de, Dehairs, Jonas, and Eggermont, Kristel
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INDUCED pluripotent stem cells ,CELL metabolism ,LIPID rafts ,CELL receptors ,PLURIPOTENT stem cells ,GENE ontology - Abstract
Charcot–Marie–Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy caused by a 1.5 Mb tandem duplication of chromosome 17 harbouring the PMP22 gene. This dose-dependent overexpression of PMP22 results in disrupted Schwann cell myelination of peripheral nerves. To obtain better insights into the underlying pathogenic mechanisms in CMT1A, we investigated the role of PMP22 duplication in cellular homeostasis in CMT1A mouse models and in patient-derived induced pluripotent stem cells differentiated into Schwann cell precursors (iPSC-SCPs). We performed lipidomic profiling and bulk RNA sequencing (RNA-seq) on sciatic nerves of two developing CMT1A mouse models and on CMT1A patient-derived iPSC-SCPs. For the sciatic nerves of the CMT1A mice, cholesterol and lipid metabolism was downregulated in a dose-dependent manner throughout development. For the CMT1A iPSC-SCPs, transcriptional analysis unveiled a strong suppression of genes related to autophagy and lipid metabolism. Gene ontology enrichment analysis identified disturbances in pathways related to plasma membrane components and cell receptor signalling. Lipidomic analysis confirmed the severe dysregulation in plasma membrane lipids, particularly sphingolipids, in CMT1A iPSC-SCPs. Furthermore, we identified reduced lipid raft dynamics, disturbed plasma membrane fluidity and impaired cholesterol incorporation and storage, all of which could result from altered lipid storage homeostasis in the patient-derived CMT1A iPSC-SCPs. Importantly, this phenotype could be rescued by stimulating autophagy and lipolysis. We conclude that PMP22 duplication disturbs intracellular lipid storage and leads to a more disordered plasma membrane owing to an alteration in the lipid composition, which might ultimately lead to impaired axo-glial interactions. Moreover, targeting lipid handling and metabolism could hold promise for the treatment of patients with CMT1A. [ABSTRACT FROM AUTHOR]
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- 2024
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4. The Influence of Lysosomal Stress on Dental Pulp Stem Cell-Derived Schwann Cells.
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Libberecht, Karen, Dirkx, Nathalie, Vangansewinkel, Tim, Vandendries, Wendy, Lambrichts, Ivo, and Wolfs, Esther
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SCHWANN cells ,DENTAL pulp ,MYELIN proteins ,HUMAN cell culture ,BLOOD proteins - Abstract
Background: Dysregulation of the endo-lysosomal–autophagy pathway has been identified as a critical factor in the pathology of various demyelinating neurodegenerative diseases, including peripheral neuropathies. This pathway plays a crucial role in transporting newly synthesized myelin proteins to the plasma membrane in myelinating Schwann cells, making these cells susceptible to lysosome-related dysfunctions. Nevertheless, the specific impact of lysosomal dysfunction in Schwann cells and its contribution to neurodegeneration remain poorly understood. Methods: We aim to mimic lysosomal dysfunction in Schwann cells using chloroquine, a lysosomal dysfunction inducer, and to monitor lysosomal leakiness, Schwann cell viability, and apoptosis over time. Additionally, due to the ethical and experimental issues associated with cell isolation and the culturing of human Schwann cells, we use human dental pulp stem cell-derived Schwann cells (DPSC-SCs) as a model in our study. Results: Chloroquine incubation boosts lysosomal presence as demonstrated by an increased Lysotracker signal. Further in-depth lysosomal analysis demonstrated an increased lysosomal size and permeability as illustrated by a TEM analysis and GAL3-LAMP1 staining. Moreover, an Alamar blue assay and Caspase-3 staining demonstrates a reduced viability and increased apoptosis, respectively. Conclusions: Our data indicate that prolonged lysosomal dysfunction leads to lysosomal permeability, reduced viability, and eventually apoptosis in human DPSC-SCs. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Dental Pulp Stem Cells: Their Potential in Reinnervation and Angiogenesis by Using Scaffolds
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Lambrichts, Ivo, Driesen, Ronald B., Dillen, Yörg, Gervois, Pascal, Ratajczak, Jessica, Vangansewinkel, Tim, Wolfs, Esther, Bronckaers, Annelies, and Hilkens, Petra
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- 2017
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6. Effect of platelet-rich and platelet-poor plasma on peri-implant innervation in dog mandibles
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Song, Dandan, Huang, Yan, Van Dessel, Jeroen, Shujaat, Sohaib, Orhan, Kaan, Vangansewinkel, Tim, Van den Eynde, Kathleen, Lambrichts, Ivo, Roskams, Tania, Politis, Constantinus, and Jacobs, Reinhilde
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- 2019
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7. Extracellular vesicle‐associated cholesterol supports the regenerative functions of macrophages in the brain.
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Vanherle, Sam, Guns, Jeroen, Loix, Melanie, Mingneau, Fleur, Dierckx, Tess, Wouters, Flore, Kuipers, Koen, Vangansewinkel, Tim, Wolfs, Esther, Lins, Paula Pincela, Bronckaers, Annelies, Lambrichts, Ivo, Dehairs, Jonas, Swinnen, Johannes V., Verberk, Sanne G. S., Haidar, Mansour, Hendriks, Jerome J. A., and Bogie, Jeroen F. J.
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CHOLESTEROL ,MACROPHAGES ,EXTRACELLULAR vesicles ,IMMUNE response ,MEMBRANE fusion ,OLIGODENDROGLIA ,CELL fusion - Abstract
Macrophages play major roles in the pathophysiology of various neurological disorders, being involved in seemingly opposing processes such as lesion progression and resolution. Yet, the molecular mechanisms that drive their harmful and benign effector functions remain poorly understood. Here, we demonstrate that extracellular vesicles (EVs) secreted by repair‐associated macrophages (RAMs) enhance remyelination ex vivo and in vivo by promoting the differentiation of oligodendrocyte precursor cells (OPCs). Guided by lipidomic analysis and applying cholesterol depletion and enrichment strategies, we find that EVs released by RAMs show markedly elevated cholesterol levels and that cholesterol abundance controls their reparative impact on OPC maturation and remyelination. Mechanistically, EV‐associated cholesterol was found to promote OPC differentiation predominantly through direct membrane fusion. Collectively, our findings highlight that EVs are essential for cholesterol trafficking in the brain and that changes in cholesterol abundance support the reparative impact of EVs released by macrophages in the brain, potentially having broad implications for therapeutic strategies aimed at promoting repair in neurodegenerative disorders. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Mouse mast cell protease 4 suppresses scar formation after traumatic spinal cord injury
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Vangansewinkel, Tim, Lemmens, Stefanie, Geurts, Nathalie, Quanten, Kirsten, Dooley, Dearbhaile, Pejler, Gunnar, and Hendrix, Sven
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- 2019
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9. The Effect of Leukocyte- and Platelet-Rich Fibrin on Central and Peripheral Nervous System Neurons—Implications for Biomaterial Applicability.
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Lambrichts, Ivo, Wolfs, Esther, Bronckaers, Annelies, Gervois, Pascal, and Vangansewinkel, Tim
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PERIPHERAL nervous system ,PLATELET-rich fibrin ,CENTRAL nervous system ,PLATELET-derived growth factor ,BRAIN-derived neurotrophic factor ,NEURAL stem cells ,REGENERATIVE medicine - Abstract
Leukocyte- 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. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Therapeutic administration of mouse mast cell protease 6 improves functional recovery after traumatic spinal cord injury in mice by promoting remyelination and reducing glial scar formation.
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Vangansewinkel, Tim, Lemmens, Stefanie, Tiane, Assia, Geurts, Nathalie, Dooley, Dearbhaile, Vanmierlo, Tim, Pejler, Gunnar, and Hendrix, Sven
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Traumatic spinal cord injury (SCI) most often leads to permanent paralysis due to the inability of axons to regenerate in the adult mammalian central nervous system (CNS). In the past, we have shown that mast cells (MCs) improve the functional outcome after SCI by suppressing scar tissue formation at the lesion site via mouse mast cell protease 6 (mMCP6). In this study, we investigated whether recombinant mMCP6 can be used therapeutically to improve the functional outcome after SCI. Therefore, we applied mMCP6 locally via an intrathecal catheter in the subacute phase after a spinal cord hemisection injury in mice. Our findings showed that hind limb motor function was significantly improved in mice that received recombinant mMCP6 compared with the vehicle‐treated group. In contrast to our previous findings in mMCP6 knockout mice, the lesion size and expression levels of the scar components fibronectin, laminin, and axon‐growth‐inhibitory chondroitin sulfate proteoglycans were not affected by the treatment with recombinant mMCP6. Surprisingly, no difference in infiltration of CD4+ T cells and reactivity of Iba‐1+ microglia/macrophages at the lesion site was observed between the mMCP6‐treated mice and control mice. Additionally, local protein levels of the pro‐ and anti‐inflammatory mediators IL‐1β, IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α, IFNγ, and MCP‐1 were comparable between the two treatment groups, indicating that locally applied mMCP6 did not affect inflammatory processes after injury. However, the increase in locomotor performance in mMCP6‐treated mice was accompanied by reduced demyelination and astrogliosis in the perilesional area after SCI. Consistently, we found that TNF‐α/IL‐1β‐astrocyte activation was decreased and that oligodendrocyte precursor cell (OPC) differentiation was increased after recombinant mMCP6 treatment in vitro. Mechanistically, this suggests effects of mMCP6 on reducing astrogliosis and improving (re)myelination in the spinal cord after injury. In conclusion, these data show for the first time that recombinant mMCP6 is therapeutically active in enhancing recovery after SCI. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Angiogenic Properties of ‘Leukocyte- and Platelet-Rich Fibrin’
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Ratajczak, Jessica, Vangansewinkel, Tim, Gervois, Pascal, Merckx, Greet, Hilkens, Petra, Quirynen, Marc, Lambrichts, Ivo, and Bronckaers, Annelies
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- 2018
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12. Targeting lipophagy in macrophages improves repair in multiple sclerosis.
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Haidar, Mansour, Loix, Melanie, Vanherle, Sam, Dierckx, Tess, Vangansewinkel, Tim, Gervois, Pascal, Wolfs, Esther, Lambrichts, Ivo, Bogie, Jeroen F.J., and Hendriks, Jerome J.A.
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TREHALOSE ,MULTIPLE sclerosis ,MYELIN basic protein ,MACROPHAGES ,STAINS & staining (Microscopy) ,NITRIC-oxide synthases - Abstract
Foamy 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. Abbreviations: Baf: bafilomycin a1; BMDM: bone marrow-derived macrophage; CD68: CD68 antigen; CNS: central nervous system; LD: lipid droplet; LIPE/HSL: lipase, hormone sensitive; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MBP: myelin basic protein; MGLL: monoglyceride lipase; MS: multiple sclerosis; NO: nitric oxide; NOS2/iNOS: nitric oxide synthase 2, inducible; ORO: oil red o; PNPLA2: patatin-like phospholipase domain containing 2; PLIN2: perilipin 2; TEM: transmission electron microscopy; TFEB: transcription factor EB; TOH: trehalose. [ABSTRACT FROM AUTHOR]
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- 2022
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13. Unraveling the Role of the Apical Papilla During Dental Root Maturation
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DRIESEN, Ronald, GERVOIS, Pascal, VANGANSEWINKEL, Tim, and LAMBRICHTS, Ivo
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SCAP ,stomatognathic system ,apical papilla ,dental ,root ,development - Abstract
The 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.
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- 2021
14. Cryopreservation and Banking of Dental Stem Cells
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Hilkens, Petra, Driesen, Ronald B., Wolfs, Esther, Gervois, Pascal, Vangansewinkel, Tim, Ratajczak, Jessica, Dillen, Yorg, Bronckaers, Annelies, and Lambrichts, Ivo
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dental stem cells ,mesenchymal stem cells ,paracrine effects ,multilineage differentiation ,cryopreservation ,dental stem cell banking ,good manufacturing practice - Abstract
Over the past decade, dental tissues have become an attractive source of mesenchymal stem cells (MSCs). Dental stem cells (DSCs) are not only able to differentiate into adipogenic, chondrogenic and osteogenic lineanges, but an increasing amount of research also pointed out their potential applicability in numerous clinical disorders, such as myocardial infarction, neurodegenerative diseases and diabetes. Together with their multilineage differentiation capacity, their easy availability from extracted third molars makes these stem cells a suitable alternative for bone marrow-derived MSCs. More importantly, DSCs appear to retain their stem cell properties following cryopreservation, a key aspect in their long-term preservation and upscale production. However, the vast number of different cryopreservation protocols makes it difficult to draw definite conclusions regarding the behavior of these stem cells. The routine application and banking of DSCs is also associated with some other pitfalls, such as interdonor variability, cell culture-induced changes and the use of animal-derived culture medium additives. Only thorough assessment of these challenges and the implementation of standardized, GMP procedures will successfully lead to better treatment options for patients who no longer benefit from current stem cell therapies.
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- 2016
15. The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental Tissue Engineering
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Ratajczak, Jessica, Bronckaers, Annelies, Dillen, Yörg, Gervois, Pascal, Vangansewinkel, Tim, Driesen, Ronald B., Wolfs, Esther, Lambrichts, Ivo, and Hilkens, Petra
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stomatognathic diseases ,Article Subject ,stomatognathic system - Abstract
Within the field of tissue engineering, natural tissues are reconstructed by combining growth factors, stem cells, and different biomaterials to serve as a scaffold for novel tissue growth. As adequate vascularization and innervation are essential components for the viability of regenerated tissues, there is a high need for easily accessible stem cells that are capable of supporting these functions. Within the human tooth and its surrounding tissues, different stem cell populations can be distinguished, such as dental pulp stem cells, stem cells from human deciduous teeth, stem cells from the apical papilla, dental follicle stem cells, and periodontal ligament stem cells. Given their straightforward and relatively easy isolation from extracted third molars, dental stem cells (DSCs) have become an attractive source of mesenchymal-like stem cells. Over the past decade, there have been numerous studies supporting the angiogenic, neuroprotective, and neurotrophic effects of the DSC secretome. Together with their ability to differentiate into endothelial cells and neural cell types, this makes DSCs suitable candidates for dental tissue engineering and nerve injury repair.
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- 2016
16. Stem Cell-Based Therapies for Ischemic Stroke: Preclinical Results and the Potential of Imaging-Assisted Evaluation of Donor Cell Fate and Mechanisms of Brain Regeneration
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Gervois, Pascal, Wolfs, Esther, Ratajczak, Jessica, Dillen, Yörg, Vangansewinkel, Tim, Hilkens, Petra, Bronckaers, Annelies, Lambrichts, Ivo, and Struys, Tom
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ischemic stroke ,mesenchymal stem cells ,induced pluripotent stem cells ,mechanisms of stem cell therapy ,noninvasive imaging - Abstract
Stroke is the second most common cause of death and is a major cause of permanent disability. Given the current demographic trend of an ageing population and associated increased risk, the prevalence of and socioeconomic burden caused by stroke will continue to rise. Current therapies are unable to sufficiently ameliorate the disease outcome and are not applicable to all patients. Therefore, strategies such as cell-based therapies with mesenchymal stem cell (MSC) or induced pluripotent stem cell (iPSC) pave the way for new treatment options for stroke. These cells showed great preclinical promise despite the fact that the precise mechanism of action and the optimal administration route are unknown. To gain dynamic insights into the underlying repair processes after stem cell engraftment, noninvasive imaging modalities were developed to provide detailed spatial and functional information on the donor cell fate and host microenvironment. This review will focus on MSCs and iPSCs as types of widely used stem cell sources in current (bio)medical research and compare their efficacy and potential to ameliorate the disease outcome in animal stroke models. In addition, novel noninvasive imaging strategies allowing temporospatial in vivo tracking of transplanted cells and coinciding evaluation of neuronal repair following stroke will be discussed. Esther Wolfs, Jessica Ratajczak, Tim Vangansewinkel, Petra Hilkens, and Annelies Bronckaers are funded by Fonds Wetenschappelijk Onderzoek by grants G0A7514N, G089213N, G029112N, 12D8516N, and 1508015N, respectively. Yorg Dillen is funded by Bijzonder On- ¨ derzoeksfonds by grant BOF15DOC04.
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- 2016
17. Preconditioning of Human Dental Pulp Stem Cells with Leukocyte- and Platelet-Rich Fibrin-Derived Factors Does Not Enhance Their Neuroregenerative Effect.
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Gervois, Pascal, Ratajczak, Jessica, Wolfs, Esther, Vangansewinkel, Tim, Dillen, Yörg, Merckx, Greet, Bronckaers, Annelies, and Lambrichts, Ivo
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DENTAL pulp ,STEM cells ,BRAIN-derived neurotrophic factor ,NEURAL stem cells ,PLATELET-rich plasma ,PLATELET-rich fibrin - Abstract
Pathologies of the central nervous system are characterized by loss of brain tissue and neuronal function which cannot be adequately restored by endogenous repair processes. This stresses the need for novel treatment options such as cell-based therapies that are able to restore damaged tissue or stimulate repair. This study investigated the neuroregenerative potential of the conditioned medium of human dental pulp stem cells (CM-hDPSCs) on neural stem cell (NSC) proliferation and migration as well as on neurite outgrowth of primary cortical neurons (pCNs). Additionally, the effect of leukocyte- and platelet-rich fibrin (L-PRF) priming on the neuroregenerative potential of the hDPSC secretome on NSCs and pCNs was evaluated. L-PRF contains factors that enhance stem cell-induced regeneration, but its effect on hDPSC-mediated neuroregeneration is unknown. This study demonstrated that CM-hDPSCs enhanced neuritogenesis. Moreover, CM-hDPSCs had a chemoattractant effect on NSCs. Although priming hDPSCs with L-PRF increased brain-derived neurotrophic factor secretion, no additional effects on the paracrine-mediated repair mechanisms were observed. These data support the neuroregenerative potential of hDPSCs, and although priming had no additional effect, the potential of L-PRF-primed hDPSCs on distinct regenerative mechanisms remains to be clarified. [ABSTRACT FROM AUTHOR]
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- 2019
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18. Late blocking of peripheral TNF-α is ineffective after spinal cord injury in mice
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Vidal, Pía M., Lemmens, Evi, Geboes, Lies, Vangansewinkel, Tim, Nelissen, Sofie, and Hendrix, Sven
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- 2013
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19. Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6.
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Vangansewinkel, Tim, Geurts, Nathalie, Quanten, Kirsten, Nelissen, Sofie, Lemmens, Stefanie, Geboes, Lies, Dooley, Dearbhaile, Vidal, Pia M., Pejler, Gunnar, and Hendrix, Sven
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SPINAL cord injuries , *MAST cell physiology , *LABORATORY mice , *PROTEOLYTIC enzymes , *CHONDROITIN sulfate proteoglycan - Abstract
An important barrier for axon regeneration and recovery after traumatic spinal cord injury (SCI) is attributed to the scar that is formed at the lesion site. Here, we investigated the effect of mouse mast cell protease (mMCP) 6, a mast cell (MC)-specific tryptase, on scarring and functional recovery after a spinal cord hemisection injury. Functional recovery was significantly impaired in both MC-deficient and mMCP6-knockout (mMCP6-/-) mice after SCI compared with wild-type control mice. This decrease in locomotor performance was associated with an increased lesion size and excessive scarring at the injury site. Axon growth-inhibitory chondroitin sulfate proteoglycans and the extracellular matrix components fibronectin, laminin, and collagen IV were significantly up-regulated in MC-deficient and mMCP6-/- mice, with an increase in scar volume between 23 and 32%. A degradation assay revealed that mMCP6 directly cleaves fibronectin and collagen IV in vitro. In addition, gene expression levels of the scar components fibronectin, aggrecan, and collagen IV were increased up to 6.8-fold in mMCP6-/- mice in the subacute phase after injury. These data indicate that endogenous mMCP6 has scar-suppressing properties after SCI via indirect cleavage of axon growth-inhibitory scar components and alteration of the gene expression profile of these factors. [ABSTRACT FROM AUTHOR]
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- 2016
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20. Mesenchymal stem cells overexpressing IL-13 decrease lesion size and demyelination after spinal cord injury
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Dooley, Dearbhaile, Lemmens, Evi, Vangansewinkel, Tim, Lemmens, Stefanie, De Vocht, Nathalie, Le Blon, Debbie, Ponsaerts, Peter, and Hendrix, Sven
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- 2014
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21. Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4.
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Nelissen, Sofie, Vangansewinkel, Tim, Geurts, Nathalie, Geboes, Lies, Lemmens, Evi, Vidal, Pia M., Lemmens, Stefanie, Willems, Leen, Boato, Francesco, Dooley, Dearbhaile, Pehl, Debora, Pejler, Gunnar, Maurer, Marcus, Metz, Martin, and Hendrix, Sven
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MAST cells , *POST-traumatic stress disorder , *SPINAL cord abnormalities , *INFLAMMATION , *LABORATORY mice , *CYTOKINES , *PROTEOLYTIC enzymes - Abstract
Abstract: Mast cells (MCs) are found abundantly in the central nervous system and play a complex role in neuroinflammatory diseases such as multiple sclerosis and stroke. In the present study, we show that MC-deficient Kit W-sh/W-sh mice display significantly increased astrogliosis and T cell infiltration as well as significantly reduced functional recovery after spinal cord injury compared to wildtype mice. In addition, MC-deficient mice show significantly increased levels of MCP-1, TNF-α, IL-10 and IL-13 protein levels in the spinal cord. Mice deficient in mouse mast cell protease 4 (mMCP4), an MC-specific chymase, also showed increased MCP-1, IL-6 and IL-13 protein levels in spinal cord samples and a decreased functional outcome after spinal cord injury. A degradation assay using supernatant from MCs derived from either mMCP4−/− mice or controls revealed that mMCP4 cleaves MCP-1, IL-6, and IL-13 suggesting a protective role for MC proteases in neuroinflammation. These data show for the first time that MCs may be protective after spinal cord injury and that they may reduce CNS damage by degrading inflammation-associated cytokines via the MC-specific chymase mMCP4. [Copyright &y& Elsevier]
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- 2014
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22. Microglia: Brain cells on the move.
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Smolders, Sophie Marie-Thérèse, Kessels, Sofie, Vangansewinkel, Tim, Rigo, Jean-Michel, Legendre, Pascal, and Brône, Bert
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MICROGLIA , *EXTRACELLULAR matrix , *CENTRAL nervous system , *CELL populations - Abstract
• Microglia are immigrant CNS immune cells that show motility and mobility, especially in the developing brain. • Microglial motility and mobility is likely steered by the constantly changing microenvironment of the CNS. • Microglia populate the developing CNS by proliferation and intensive migration, of which the molecular mechanisms have just started to be unravelled. • Microglia actively participate in CNS development and homeostasis, even at early developmental stages. • Defective microglial functions during development can be related to neurodevelopmental disorders. In the last decade, tremendous progress has been made in understanding the biology of microglia – i.e. the fascinating immigrated resident immune cell population of the central nervous system (CNS). Recent literature reviews have largely dealt with the plentiful functions of microglia in CNS homeostasis, development and pathology, and the influences of sex and the microbiome. In this review, the intriguing aspect of their physical plasticity during CNS development will get specific attention. Microglia move around (mobility) and reshape their processes (motility). Microglial migration into and inside the CNS is most prominent throughout development and consequently most of the data described in this review concern mobility and motility in the changing environment of the developing brain. Here, we first define microglia based on their highly specialized age- and region-dependent gene expression signature and associated functional heterogeneity. Next, we describe their origin, the migration route of immature microglial cells towards the CNS, the mechanisms underlying their invasion of the CNS, and their spatiotemporal localization and surveying behaviour inside the developing CNS. These processes are dependent on microglial mobility and motility which are determined by the microenvironment of the CNS. Therefore, we further zoom in on the changing environment during CNS development. We elaborate on the extracellular matrix and the respective integrin receptors on microglia and we discuss the purinergic and molecular signalling in microglial mobility. In the last section, we discuss the physiological and pathological functions of microglia in which mobility and motility are involved to stress the importance of microglial 'movement'. [ABSTRACT FROM AUTHOR]
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- 2019
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23. Therapeutic administration of mouse mast cell protease 6 improves functional recovery after traumatic spinal cord injury in mice by promoting remyelination and reducing glial scar formation
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Tim Vangansewinkel, Stefanie Lemmens, Assia Tiane, Nathalie Geurts, Dearbhaile Dooley, Tim Vanmierlo, Gunnar Pejler, Sven Hendrix, Hendrix, Sven/0000-0003-2344-7369, VANGANSEWINKEL, Tim, LEMMENS, Stefanie, TIANE, Assia, GEURTS, Nathalie, DOOLEY, Dearbhaile, VANMIERLO, Tim, Pejler, Gunnar, and HENDRIX, Sven
- Subjects
AXONAL REGENERATION ,REPAIR ,NEUROPROTECTION ,therapy ,recombinant mMCP6 ,functional recovery ,Neurosciences ,ASTROCYTES ,Biochemistry ,spinal cord injury ,ACTIVATION ,mast cell proteases ,PATHOLOGY ,METALLOPROTEINASES ,INFLAMMATION ,astrogliosis ,Genetics ,demyelination ,BRAIN ,Molecular Biology ,Neurovetenskaper ,Biotechnology - Abstract
Traumatic spinal cord injury (SCI) most often leads to permanent paralysis due to the inability of axons to regenerate in the adult mammalian central nervous system (CNS). In the past, we have shown that mast cells (MCs) improve the functional outcome after SCI by suppressing scar tissue formation at the lesion site via mouse mast cell protease 6 (mMCP6). In this study, we investigated whether recombinant mMCP6 can be used therapeutically to improve the functional outcome after SCI. Therefore, we applied mMCP6 locally via an intrathecal catheter in the subacute phase after a spinal cord hemisection injury in mice. Our findings showed that hind limb motor function was significantly improved in mice that received recombinant mMCP6 compared with the vehicle-treated group. In contrast to our previous findings in mMCP6 knockout mice, the lesion size and expression levels of the scar components fibronectin, laminin, and axon-growth-inhibitory chondroitin sulfate proteoglycans were not affected by the treatment with recombinant mMCP6. Surprisingly, no difference in infiltration of CD4+ T cells and reactivity of Iba-1+ microglia/macrophages at the lesion site was observed between the mMCP6-treated mice and control mice. Additionally, local protein levels of the pro-and anti-inflammatory mediators IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN gamma, and MCP-1 were comparable between the two treatment groups, indicating that locally applied mMCP6 did not affect inflammatory processes after injury. However, the increase in locomotor performance in mMCP6-treated mice was accompanied by reduced demyelination and astrogliosis in the perilesional area after SCI. Consistently, we found that TNF-alpha/IL-1 beta-astrocyte activation was decreased and that oligodendrocyte precursor cell (OPC) differentiation was increased after recombinant mMCP6 treatment in vitro. Mechanistically, this suggests effects of mMCP6 on reducing astrogliosis and improving (re)myelination in the spinal cord after injury. In conclusion, these data show for the first time that recombinant mMCP6 is therapeutically active in enhancing recovery after SCI. Agentschap voor Innovatie door Wetenschap en Technologie, Grant/ Award Number: 101517; Fonds voor Wetenschappelijk OnderzoekVlaanderen, Grant/Award Number: G067715N, G091518N and G0C2120N
- Published
- 2023
24. Effect of platelet-rich and platelet-poor plasma on peri-implant innervation in dog mandibles
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Ivo Lambrichts, Dandan Song, Kaan Orhan, Kathleen Van den Eynde, Yan Huang, Tania Roskams, Jeroen Van Dessel, Tim Vangansewinkel, Constantinus Politis, Reinhilde Jacobs, Sohaib Shujaat, Lambrichts, Ivo/0000-0001-7520-0021, SONG, Dandan, Huang, Yan, Van Dessel, Jeroen, Shujaat, Sohaib, Orhan, Kaan, VANGANSEWINKEL, Tim, Van den Eynde, Kathleen, LAMBRICHTS, Ivo, Roskams, Tania, POLITIS, Constantinus, and Jacobs, Reinhilde
- Subjects
medicine.medical_specialty ,Myelinated nerve fiber ,Dental implant ,medicine.medical_treatment ,Platelet-poor plasma ,lcsh:Medicine ,Beagle ,03 medical and health sciences ,0302 clinical medicine ,Platelet-rich plasma ,Internal medicine ,Medicine ,Platelet ,Myelinated nerve fibers ,Histomorphometry ,business.industry ,Research ,Innervation ,lcsh:R ,030206 dentistry ,lcsh:RK1-715 ,Endocrinology ,lcsh:Dentistry ,030220 oncology & carcinogenesis ,Animal studies ,Implant ,business - Abstract
Background: Autologous plasma fractions, such as platelet-rich plasma (PRP) and platelet-poor plasma (PPP), contain growth factors that can enhance neural cell survival and are therefore likely to have the ability to promote nerve regeneration. The present study compared the effect of PRP and PPP application on myelinated nerve density and diameter in the peri-implant bone region. In addition, the effect of healing time on nerve regeneration was assessed. Materials and methods: Nine beagle dogs randomly received 54 dental implants in the bilateral mandible according to a split-mouth design. Each implant was randomly assigned to one of three implant protocols: delayed implant placement with delayed loading (DIP + DL) with local application of PRP, DIP + DL with local application of PPP and DIP + DL without any plasma additive. The animals were euthanized at 1, 3, and 6 months after loading (3 dogs per time point). Block biopsies were prepared for histomorphometry in the peri-implant bone within 500 mu m around the implants. Results: Myelinated nerve fibers were identified in the trabecular bone and in the osteons near the implants surface. The nerve fibers in the PRP group (median +/- IQR; 2.88 +/- 1.55 mu m) had a significantly (p < 0.05) greater diameter compared to the PPP (2.40 +/- 0.91 mu m) and control (2.11 +/- 1.16 mu m) group. The nerve diameter after 6 months healing (3.18 +/- 1.58 mu m) was significantly (p < 0.05) greater compared to 1 (2.08 +/- 0.89 mu m) and 3 (2.49 +/- 1.22 mu m) months. No significant difference was found for myelinated nerve density between groups and healing time. Conclusions: The present study showed that the healing time significantly influenced the diameter of the myelinated nerve fibers in peri-implant bone. PRP exerted a significant effect on the diameter of the myelinated nerve fibers as compared to PPP. Large-scale animal studies and longer follow-up periods are needed to confirm these findings and to verify whether platelet plasma can facilitate nerve regeneration process. This work was supported by a Sichuan Province Science and Technology Support Program (2016SZ0010). DS received fellowship support from the China Scholarship Council (201708210187). HY is a postdoctoral (11.N3.615N) and JVD is a predoctoral (11.ZU.117N) FWO-research fellow. Song, DD (reprint author), Katholieke Univ Leuven, OMFS IMPATH Res Grp, Dept Imaging & Pathol, Fac Med, Campus Sint Rafael,Kapucijnenvoer 33, BE-3000 Leuven, Belgium; Univ Hosp Leuven, Oral & Maxillofacial Surg, Campus Sint Rafael,Kapucijnenvoer 33, BE-3000 Leuven, Belgium. dandansong9015@gmail.com
- Published
- 2019
25. Mouse mast cell protease 4 suppresses scar formation after traumatic spinal cord injury
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Kirsten Quanten, Nathalie Geurts, Tim Vangansewinkel, Sven Hendrix, Stefanie Lemmens, Gunnar Pejler, Dearbhaile Dooley, VANGANSEWINKEL, Tim, LEMMENS, Stefanie, GEURTS, Nathalie, Quanten, Kirsten, DOOLEY, Dearbhaile, Pejler, Gunnar, and HENDRIX, Sven
- Subjects
0301 basic medicine ,lcsh:Medicine ,Article ,Lesion ,03 medical and health sciences ,Cicatrix ,Mice ,0302 clinical medicine ,Chymases ,Neurocan ,Laminin ,In vivo ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,Mast Cells ,lcsh:Science ,Spinal cord injury ,Spinal Cord Injuries ,Multidisciplinary ,biology ,Chemistry ,lcsh:R ,Serine Endopeptidases ,Chymase ,Immunology in the medical area ,medicine.disease ,Spinal cord ,Fibrosis ,Cell biology ,Fibronectins ,Nerve Regeneration ,Fibronectin ,030104 developmental biology ,medicine.anatomical_structure ,Chondroitin Sulfate Proteoglycans ,Spinal Cord ,Immunologi inom det medicinska området ,biology.protein ,lcsh:Q ,medicine.symptom ,Neuroglia ,030217 neurology & neurosurgery - Abstract
Spinal cord injury (SCI) triggers the formation of a glial and fibrotic scar, which creates a major barrier for neuroregenerative processes. Previous findings indicate that mast cells (MCs) protect the spinal cord after mechanical damage by suppressing detrimental inflammatory processes via mouse mast cell protease 4 (mMCP4), a MC-specific chymase. In addition to these immunomodulatory properties, mMCP4 also plays an important role in tissue remodeling and extracellular matrix degradation. Therefore, we have investigated the effects of mMCP4 on the scarring response after SCI. We demonstrate that the decrease in locomotor performance in mMCP4(-/-) mice is correlated with excessive scar formation at the lesion. The expression of axon-growth inhibitory chondroitin sulfate proteoglycans was dramatically increased in the perilesional area in mMCP4(-/-) mice compared to wild type mice. Moreover, the fibronectin-, laminin-, and collagen IV-positive scar was significantly enlarged in mMCP4(-/-) mice at the lesion center. A degradation assay revealed that mMCP4 directly cleaves collagen IV in vitro. On the gene expression level, neurocan and GFAP were significantly higher in the mMCP4(-/-) group at day 2 and day 28 after injury respectively. In contrast, the expression of fibronectin and collagen IV was reduced in mMCP4(-/-) mice compared to WT mice at day 7 after SCI. In conclusion, our data show that mMCP4 modulates scar development after SCI by altering the gene and protein expression patterns of key scar factors in vivo. Therefore, we suggest a new mechanism via which endogenous mMCP4 can improve recovery after SCI. The authors thank Leen Timmermans (Hasselt University) for her help with the qPCR analysis. This study was supported by grants from Fund for Scientific Research Flanders (FWO-Vlaanderen) to S.H. (G.0389.12, G0A5813) and N.G. (1.2.917.14N), and from 'Agency for Innovation by Science and Technology in Flanders' (IWT-Vlaanderen) to T.V. (101517) and S.L. (131230).
- Published
- 2019
26. PMP22 duplication dysregulates lipid homeostasis and plasma membrane organization in developing human Schwann cells.
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Prior R, Silva A, Vangansewinkel T, Idkowiak J, Tharkeshwar AK, Hellings TP, Michailidou I, Vreijling J, Loos M, Koopmans B, Vlek N, Agaser C, Kuipers TB, Michiels C, Rossaert E, Verschoren S, Vermeire W, de Laat V, Dehairs J, Eggermont K, van den Biggelaar D, Bademosi AT, Meunier FA, vandeVen M, Van Damme P, Mei H, Swinnen JV, Lambrichts I, Baas F, Fluiter K, Wolfs E, and Van Den Bosch L
- Subjects
- Animals, Humans, Mice, Gene Duplication, Sciatic Nerve metabolism, Cell Membrane metabolism, Charcot-Marie-Tooth Disease genetics, Charcot-Marie-Tooth Disease metabolism, Charcot-Marie-Tooth Disease pathology, Homeostasis physiology, Induced Pluripotent Stem Cells metabolism, Lipid Metabolism physiology, Myelin Proteins metabolism, Myelin Proteins genetics, Schwann Cells metabolism
- Abstract
Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy caused by a 1.5 Mb tandem duplication of chromosome 17 harbouring the PMP22 gene. This dose-dependent overexpression of PMP22 results in disrupted Schwann cell myelination of peripheral nerves. To obtain better insights into the underlying pathogenic mechanisms in CMT1A, we investigated the role of PMP22 duplication in cellular homeostasis in CMT1A mouse models and in patient-derived induced pluripotent stem cells differentiated into Schwann cell precursors (iPSC-SCPs). We performed lipidomic profiling and bulk RNA sequencing (RNA-seq) on sciatic nerves of two developing CMT1A mouse models and on CMT1A patient-derived iPSC-SCPs. For the sciatic nerves of the CMT1A mice, cholesterol and lipid metabolism was downregulated in a dose-dependent manner throughout development. For the CMT1A iPSC-SCPs, transcriptional analysis unveiled a strong suppression of genes related to autophagy and lipid metabolism. Gene ontology enrichment analysis identified disturbances in pathways related to plasma membrane components and cell receptor signalling. Lipidomic analysis confirmed the severe dysregulation in plasma membrane lipids, particularly sphingolipids, in CMT1A iPSC-SCPs. Furthermore, we identified reduced lipid raft dynamics, disturbed plasma membrane fluidity and impaired cholesterol incorporation and storage, all of which could result from altered lipid storage homeostasis in the patient-derived CMT1A iPSC-SCPs. Importantly, this phenotype could be rescued by stimulating autophagy and lipolysis. We conclude that PMP22 duplication disturbs intracellular lipid storage and leads to a more disordered plasma membrane owing to an alteration in the lipid composition, which might ultimately lead to impaired axo-glial interactions. Moreover, targeting lipid handling and metabolism could hold promise for the treatment of patients with CMT1A., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2024
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27. Unraveling the Role of the Apical Papilla During Dental Root Maturation.
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Driesen RB, Gervois P, Vangansewinkel T, and Lambrichts I
- Abstract
The 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Driesen, Gervois, Vangansewinkel and Lambrichts.)
- Published
- 2021
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28. Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha.
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Driesen RB, Hilkens P, Smisdom N, Vangansewinkel T, Dillen Y, Ratajczak J, Wolfs E, Gervois P, Ameloot M, Bronckaers A, and Lambrichts I
- Abstract
Fibroblast activation protein-α (FAPα) is a membrane protein with dipeptidyl-peptidase and type I collagenase activity and is expressed during fetal growth. At the age of adolescence, FAPα expression is greatly reduced, only emerging in pathologies associated with extracellular matrix remodeling. We determined whether FAPα is expressed in human dental tissue involved in root maturation i.e., dental follicle and apical papilla and in dental pulp tissue. The dental follicle revealed a high concentration of FAPα and vimentin-positive cells within the stromal tissue. A similar observation was made in cell culture and FACS analysis confirmed these as dental follicle stem cells. Within the remnants of the Hertwigs' epithelial root sheath, we observed FAPα staining in the E-cadherin positive and vimentin-negative epithelial islands. FAPα- and vimentin-positive cells were encountered at the periphery of the islands suggesting an epithelial mesenchymal transition process. Analysis of the apical papilla revealed two novel histological regions; the periphery with dense and parallel aligned collagen type I defined as cortex fibrosa and the inner stromal tissue composed of less compacted collagen defined as medulla. FAPα expression was highly present within the medulla suggesting a role in extracellular matrix remodeling. Dental pulp tissue uncovered a heterogeneous FAPα staining but strong staining was noted within odontoblasts. In vitro studies confirmed the presence of FAPα expression in stem cells of the apical papilla and dental pulp. This study identified the expression of FAPα expression in dental stem cells which could open new perspectives in understanding dental root maturation and odontoblast function., (Copyright © 2020 Driesen, Hilkens, Smisdom, Vangansewinkel, Dillen, Ratajczak, Wolfs, Gervois, Ameloot, Bronckaers and Lambrichts.)
- Published
- 2020
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29. Cell-Based Delivery of Interleukin-13 Directs Alternative Activation of Macrophages Resulting in Improved Functional Outcome after Spinal Cord Injury.
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Dooley D, Lemmens E, Vangansewinkel T, Le Blon D, Hoornaert C, Ponsaerts P, and Hendrix S
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- Animals, Axons drug effects, Axons pathology, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes immunology, Cell Count, Demyelinating Diseases pathology, Demyelinating Diseases physiopathology, Interleukin-13 pharmacology, Interleukin-13 therapeutic use, Macrophages drug effects, Macrophages pathology, Mice, Inbred BALB C, Mice, Inbred C57BL, Microglia drug effects, Microglia pathology, Neuroprotective Agents pharmacology, Neuroprotective Agents therapeutic use, Recovery of Function drug effects, Spinal Cord Injuries immunology, Spinal Cord Injuries pathology, Treatment Outcome, Interleukin-13 administration & dosage, Macrophage Activation drug effects, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells metabolism, Spinal Cord Injuries physiopathology, Spinal Cord Injuries therapy
- Abstract
The therapeutic effects of mesenchymal stem cell (MSC) transplantation following spinal cord injury (SCI) to date have been limited. Therefore, we aimed to enhance the immunomodulatory properties of MSCs via continuous secretion of the anti-inflammatory cytokine interleukin-13 (IL-13). By using MSCs as carriers of IL-13 (MSC/IL-13), we investigated their therapeutic potential, compared with non-engineered MSCs, in a mouse model of SCI. We show that transplanted MSC/IL-13 significantly improve functional recovery following SCI, and also decrease lesion size and demyelinated area by more than 40%. Further histological analyses in CX
3 CR1EGFP/+ CCR2RFP/+ transgenic mice indicated that MSC/IL-13 significantly decrease the number of resident microglia and increase the number of alternatively activated macrophages. In addition, the number of macrophage-axon contacts in MSC/IL-13-treated mice was decreased by 50%, suggesting a reduction in axonal dieback. Our data provide evidence that transplantation of MSC/IL-13 leads to improved functional and histopathological recovery in a mouse model of SCI., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2016
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30. Stem Cell-Based Therapies for Ischemic Stroke: Preclinical Results and the Potential of Imaging-Assisted Evaluation of Donor Cell Fate and Mechanisms of Brain Regeneration.
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Gervois P, Wolfs E, Ratajczak J, Dillen Y, Vangansewinkel T, Hilkens P, Bronckaers A, Lambrichts I, and Struys T
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- Animals, Brain Ischemia diagnostic imaging, Brain Ischemia pathology, Humans, Induced Pluripotent Stem Cells transplantation, Luminescent Measurements methods, Magnetic Resonance Imaging methods, Mesenchymal Stem Cell Transplantation methods, Positron-Emission Tomography methods, Regeneration physiology, Stroke diagnostic imaging, Stroke pathology, Tomography, Emission-Computed, Single-Photon methods, Brain Ischemia therapy, Stem Cell Transplantation methods, Stroke therapy
- Abstract
Stroke is the second most common cause of death and is a major cause of permanent disability. Given the current demographic trend of an ageing population and associated increased risk, the prevalence of and socioeconomic burden caused by stroke will continue to rise. Current therapies are unable to sufficiently ameliorate the disease outcome and are not applicable to all patients. Therefore, strategies such as cell-based therapies with mesenchymal stem cell (MSC) or induced pluripotent stem cell (iPSC) pave the way for new treatment options for stroke. These cells showed great preclinical promise despite the fact that the precise mechanism of action and the optimal administration route are unknown. To gain dynamic insights into the underlying repair processes after stem cell engraftment, noninvasive imaging modalities were developed to provide detailed spatial and functional information on the donor cell fate and host microenvironment. This review will focus on MSCs and iPSCs as types of widely used stem cell sources in current (bio)medical research and compare their efficacy and potential to ameliorate the disease outcome in animal stroke models. In addition, novel noninvasive imaging strategies allowing temporospatial in vivo tracking of transplanted cells and coinciding evaluation of neuronal repair following stroke will be discussed., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
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31. Basophils are dispensable for the recovery of gross locomotion after spinal cord hemisection injury.
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Geurts N, Vangansewinkel T, Lemmens S, Nelissen S, Geboes L, Schwartz C, Voehringer D, and Hendrix S
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- Animals, Basophils pathology, Mice, Mice, Transgenic, Spinal Cord Injuries pathology, Spinal Cord Injuries physiopathology, Basophils immunology, Locomotion, Recovery of Function immunology, Spinal Cord Injuries immunology
- Abstract
Basophils are the smallest population of granulocytes found in the circulation. They have crucial and nonredundant roles in allergic disorders, in protection from parasite infections, in autoimmunity, and in the regulation of type 2 immunity. They share phenotypic and functional properties with mast cells, which exert substantial protective effects after traumatic brain injury and spinal cord injury, although they are considered one of the most proinflammatory cell types in the body. In contrast, the in vivo functions of basophils in central nervous system trauma are still obscure and not well studied. In this study, we show that by comparing spinal cord injury in wild type vs. basophil-deficient Mcpt8Cre transgenic mice, the locomotor recovery is not affected in mice depleted in basophils. In addition, no substantial differences were observed in the lesion size and in the astrocytic and macrophage/microglia reaction between both mouse strains. Hence, despite the multiple properties shared with mast cells, these data show, for the first time, to our knowledge, that basophils are dispensable for the functional recovery process after hemisection injury to the spinal cord in mice., (© Society for Leukocyte Biology.)
- Published
- 2016
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32. The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental Tissue Engineering.
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Ratajczak J, Bronckaers A, Dillen Y, Gervois P, Vangansewinkel T, Driesen RB, Wolfs E, Lambrichts I, and Hilkens P
- Abstract
Within the field of tissue engineering, natural tissues are reconstructed by combining growth factors, stem cells, and different biomaterials to serve as a scaffold for novel tissue growth. As adequate vascularization and innervation are essential components for the viability of regenerated tissues, there is a high need for easily accessible stem cells that are capable of supporting these functions. Within the human tooth and its surrounding tissues, different stem cell populations can be distinguished, such as dental pulp stem cells, stem cells from human deciduous teeth, stem cells from the apical papilla, dental follicle stem cells, and periodontal ligament stem cells. Given their straightforward and relatively easy isolation from extracted third molars, dental stem cells (DSCs) have become an attractive source of mesenchymal-like stem cells. Over the past decade, there have been numerous studies supporting the angiogenic, neuroprotective, and neurotrophic effects of the DSC secretome. Together with their ability to differentiate into endothelial cells and neural cell types, this makes DSCs suitable candidates for dental tissue engineering and nerve injury repair.
- Published
- 2016
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33. Cryopreservation and Banking of Dental Stem Cells.
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Hilkens P, Driesen RB, Wolfs E, Gervois P, Vangansewinkel T, Ratajczak J, Dillen Y, Bronckaers A, and Lambrichts I
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- Cell Differentiation, Cell Proliferation, Cryoprotective Agents pharmacology, Culture Media pharmacology, Dental Pulp drug effects, Dental Pulp physiology, Diabetes Mellitus pathology, Diabetes Mellitus therapy, Dimethyl Sulfoxide pharmacology, Humans, Insulin-Secreting Cells physiology, Insulin-Secreting Cells transplantation, Myocardial Infarction pathology, Myocardial Infarction therapy, Myocytes, Cardiac physiology, Myocytes, Cardiac transplantation, Neurodegenerative Diseases pathology, Neurodegenerative Diseases therapy, Neurons physiology, Neurons transplantation, Stem Cells drug effects, Stem Cells physiology, Biological Specimen Banks organization & administration, Cryopreservation methods, Dental Pulp cytology, Insulin-Secreting Cells cytology, Myocytes, Cardiac cytology, Neurons cytology, Stem Cells cytology
- Abstract
Over the past decade, dental tissues have become an attractive source of mesenchymal stem cells (MSCs). Dental stem cells (DSCs) are not only able to differentiate into adipogenic, chondrogenic and osteogenic lineanges, but an increasing amount of research also pointed out their potential applicability in numerous clinical disorders, such as myocardial infarction, neurodegenerative diseases and diabetes. Together with their multilineage differentiation capacity, their easy availability from extracted third molars makes these stem cells a suitable alternative for bone marrow-derived MSCs. More importantly, DSCs appear to retain their stem cell properties following cryopreservation, a key aspect in their long-term preservation and upscale production. However, the vast number of different cryopreservation protocols makes it difficult to draw definite conclusions regarding the behavior of these stem cells. The routine application and banking of DSCs is also associated with some other pitfalls, such as interdonor variability, cell culture-induced changes and the use of animal-derived culture medium additives. Only thorough assessment of these challenges and the implementation of standardized, GMP procedures will successfully lead to better treatment options for patients who no longer benefit from current stem cell therapies.
- Published
- 2016
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