104 results on '"Wolfs, Esther"'
Search Results
2. Carnosine synthase deficiency aggravates neuroinflammation in multiple sclerosis
- Author
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Spaas, Jan, Van der Stede, Thibaux, de Jager, Sarah, van de Waterweg Berends, Annet, Tiane, Assia, Baelde, Hans, Baba, Shahid P., Eckhardt, Matthias, Wolfs, Esther, Vanmierlo, Tim, Hellings, Niels, Eijnde, Bert O., and Derave, Wim
- Published
- 2023
- Full Text
- View/download PDF
3. Proteostasis plays an important role in demyelinating Charcot Marie Tooth disease
- Author
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Libberecht, Karen, Vangansewinkel, Tim, Van Den Bosch, Ludo, Lambrichts, Ivo, and Wolfs, Esther
- Published
- 2023
- Full Text
- View/download PDF
4. Selective PDE4 subtype inhibition provides new opportunities to intervene in neuroinflammatory versus myelin damaging hallmarks of multiple sclerosis
- Author
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Schepers, Melissa, Paes, Dean, Tiane, Assia, Rombaut, Ben, Piccart, Elisabeth, van Veggel, Lieve, Gervois, Pascal, Wolfs, Esther, Lambrichts, Ivo, Brullo, Chiara, Bruno, Olga, Fedele, Ernesto, Ricciarelli, Roberta, ffrench-Constant, Charles, Bechler, Marie E., van Schaik, Pauline, Baron, Wia, Lefevere, Evy, Wasner, Kobi, Grünewald, Anne, Verfaillie, Catherine, Baeten, Paulien, Broux, Bieke, Wieringa, Paul, Hellings, Niels, Prickaerts, Jos, and Vanmierlo, Tim
- Published
- 2023
- Full Text
- View/download PDF
5. Safety and Homing of Human Dental Pulp Stromal Cells in Head and Neck Cancer
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Merckx, Greet, Lo Monaco, Melissa, Lambrichts, Ivo, Himmelreich, Uwe, Bronckaers, Annelies, and Wolfs, Esther
- Published
- 2021
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6. The Influence of Lysosomal Stress on Dental Pulp Stem Cell-Derived Schwann Cells.
- Author
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Libberecht, Karen, Dirkx, Nathalie, Vangansewinkel, Tim, Vandendries, Wendy, Lambrichts, Ivo, and Wolfs, Esther
- Subjects
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]
- Published
- 2024
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7. Charting progress towards system-scale ecosystem service valuation in islands
- Author
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OLESON, KIRSTEN L.L., GRAFELD, SHANNA, VAN BEUKERING, PIETER, BRANDER, LUKE, JAMES, PHILIP A.S., and WOLFS, ESTHER
- Published
- 2018
8. Adult Neurogenesis in the Subventricular Zone and Its Regulation After Ischemic Stroke: Implications for Therapeutic Approaches
- Author
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Dillen, Yörg, Kemps, Hannelore, Gervois, Pascal, Wolfs, Esther, and Bronckaers, Annelies
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- 2020
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9. The sphingosine‐1‐phosphate receptor 1 modulator ponesimod repairs cuprizone‐induced demyelination and induces oligodendrocyte differentiation.
- Author
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Willems, Emily, Schepers, Melissa, Piccart, Elisabeth, Wolfs, Esther, Hellings, Niels, Ait‐Tihyaty, Maria, and Vanmierlo, Tim
- Published
- 2024
- Full Text
- View/download PDF
10. Pyridoxamine Attenuates Doxorubicin-Induced Cardiomyopathy without Affecting Its Antitumor Effect on Rat Mammary Tumor Cells.
- Author
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Haesen, Sibren, Verghote, Eline, Heeren, Ellen, Wolfs, Esther, Deluyker, Dorien, and Bito, Virginie
- Subjects
DOXORUBICIN ,SPRAGUE Dawley rats ,CARDIOMYOPATHIES ,VITAMIN B6 ,VENTRICULAR ejection fraction ,CYTOTOXINS ,CELL survival - Abstract
Doxorubicin (DOX) is commonly used in cancer treatment but associated with cardiotoxicity. Pyridoxamine (PM), a vitamin B6 derivative, could be a cardioprotectant. This study investigated the effect of PM on DOX cardiotoxicity and DOX antitumor effectiveness. Sprague Dawley rats were treated intravenously with DOX (2 mg/kg/week) or saline over eight weeks. Two other groups received PM via oral intake (1 g/L in water bottles) next to DOX or saline. Echocardiography was performed after eight weeks. PM treatment significantly attenuated the DOX-induced reduction in left ventricular ejection fraction (72 ± 2% vs. 58 ± 3% in DOX; p < 0.001) and increase in left ventricular end-systolic volume (0.24 ± 0.02 µL/cm
2 vs. 0.38 ± 0.03 µL/cm2 in DOX; p < 0.0001). Additionally, LA7 tumor cells were exposed to DOX, PM, or DOX and PM for 24 h, 48 h, and 72 h. Cell viability, proliferation, cytotoxicity, and apoptosis were assessed. DOX significantly reduced LA7 cell viability and proliferation (p < 0.0001) and increased cytotoxicity (p < 0.05) and cleaved caspase-3 (p < 0.001). Concomitant PM treatment did not alter the DOX effect on LA7 cells. In conclusion, PM attenuated DOX-induced cardiomyopathy in vivo without affecting the antitumor effect of DOX in vitro, highlighting PM as a promising cardioprotectant for DOX-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]- Published
- 2024
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11. Pyridoxamine Limits Cardiac Dysfunction in a Rat Model of Doxorubicin-Induced Cardiotoxicity.
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Haesen, Sibren, Jager, Manon Marie, Brillouet, Aline, de Laat, Iris, Vastmans, Lotte, Verghote, Eline, Delaet, Anouk, D'Haese, Sarah, Hamad, Ibrahim, Kleinewietfeld, Markus, Mebis, Jeroen, Mullens, Wilfried, Lambrichts, Ivo, Wolfs, Esther, Deluyker, Dorien, and Bito, Virginie
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HEART diseases ,CARDIOTOXICITY ,ANIMAL disease models ,SPRAGUE Dawley rats ,VITAMIN B6 - Abstract
The use of doxorubicin (DOX) chemotherapy is restricted due to dose-dependent cardiotoxicity. Pyridoxamine (PM) is a vitamin B6 derivative with favorable effects on diverse cardiovascular diseases, suggesting a cardioprotective effect on DOX-induced cardiotoxicity. The cardioprotective nature of PM was investigated in a rat model of DOX-induced cardiotoxicity. Six-week-old female Sprague Dawley rats were treated intravenously with 2 mg/kg DOX or saline (CTRL) weekly for eight weeks. Two other groups received PM via the drinking water next to DOX (DOX+PM) or saline (CTRL+PM). Echocardiography, strain analysis, and hemodynamic measurements were performed to evaluate cardiac function. Fibrotic remodeling, myocardial inflammation, oxidative stress, apoptosis, and ferroptosis were evaluated by various in vitro techniques. PM significantly attenuated DOX-induced left ventricular (LV) dilated cardiomyopathy and limited TGF-β1-related LV fibrotic remodeling and macrophage-driven myocardial inflammation. PM protected against DOX-induced ferroptosis, as evidenced by restored DOX-induced disturbance of redox balance, improved cytosolic and mitochondrial iron regulation, and reduced mitochondrial damage at the gene level. In conclusion, PM attenuated the development of cardiac damage after DOX treatment by reducing myocardial fibrosis, inflammation, and mitochondrial damage and by restoring redox and iron regulation at the gene level, suggesting that PM may be a novel cardioprotective strategy for DOX-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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12. Extracellular vesicle‐associated cholesterol supports the regenerative functions of macrophages in the brain.
- Author
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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]
- Published
- 2023
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13. 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
- Published
- 2017
- Full Text
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14. Multipotent adult progenitor cells improve the hematopoietic function in myelodysplasia
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Roobrouck, Valerie D., Wolfs, Esther, Delforge, Michel, Broekaert, Dorien, Chakraborty, Soumen, Sels, Kathleen, Vanwelden, Thomas, Holvoet, Bryan, Lhoest, Larissa, Khurana, Satish, Pandey, Shubham, Hoornaert, Chloé, Ponsaerts, Peter, Struys, Tom, Boeckx, Nancy, Vandenberghe, Peter, Deroose, Christophe M., and Verfaillie, Catherine M.
- Published
- 2017
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15. The Effect of Leukocyte- and Platelet-Rich Fibrin on Central and Peripheral Nervous System Neurons—Implications for Biomaterial Applicability.
- Author
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Lambrichts, Ivo, Wolfs, Esther, Bronckaers, Annelies, Gervois, Pascal, and Vangansewinkel, Tim
- Subjects
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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]
- Published
- 2023
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16. Phloretin enhances remyelination by stimulating oligodendrocyte precursor cell differentiation.
- Author
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Dierckx, Tess, Vanherle, Sam, Haidar, Mansour, Grajchen, Elien, Mingneau, Fleur, Gervois, Pascal, Wolfs, Esther, Bylemans, Dany, Voet, Arnout, Tien Nguyen, Hamad, Ibrahim, Kleinewietfeld, Markus, Bogie, Jeroen F. J., and Hendriks, Jerome J. A.
- Subjects
PHLORETIN ,PEROXISOME proliferator-activated receptors ,CELL differentiation ,CENTRAL nervous system ,DEMYELINATION ,REMANUFACTURING - Abstract
Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Why endogenous repair mechanisms frequently fail in these disorders is poorly understood. However, there is now evidence indicating 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 toward an antiinflammatory phenotype. Here, we show that phloretin also markedly stimulates remyelination in ex vivo and in vivo animal models. Improved remyelination was attributed to a direct impact of phloretin on OPC maturation and occurred independently from alterations in microglia function and inflammation. We found, mechanistically, that phloretin acts as a direct ligand for the fatty acid sensing nuclear receptor peroxisome proliferator-activated receptor gamma, thereby promoting the maturation of OPCs. Together, our findings indicate that phloretin has proregenerative properties in central nervous system disorders, with potentially broad implications for the development of therapeutic strategies and dietary interventions aimed at promoting remyelination. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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17. Targeting lipophagy in macrophages improves repair in multiple sclerosis.
- Author
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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]
- Published
- 2022
- Full Text
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18. Radiolabeling Strategies for Radionuclide Imaging of Stem Cells
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Wolfs, Esther, Verfaillie, Catherine M., Van Laere, Koen, and Deroose, Christophe M.
- Published
- 2015
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19. Brown Boobies (Sula leucogaster) roosting at Washington-Slagbaai National Park, Bonaire, Caribbean Netherlands.
- Author
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Simal, Fernando, Vallarino, Adriana, Beukenboom, Elsmarie, Paula, Rutsel, Beaumont, Henry, Zaragoza, George, Wolfs, Esther, Holian, Patrick, and Albers, Elisabeth
- Abstract
Copyright of Journal of Caribbean Ornithology is the property of Society for the Conservation & Study of Caribbean Birds and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2020
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20. The Economic Value of the Coral Reefs of Saipan, Commonwealth of the Northern Mariana Islands
- Author
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van Beukering, Pieter, Haider, W., WOLFS, ESTHER, Liu, Y., van der Leeuw, Kim, Longland, M., Sablan, J., Beardmore, B., Di Prima, S.L., Massey, Eric, Cesar, H.S.J., and Hausfather, Zeke
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Coral reefs ,Spatial analysis ,Economic ,Saipan - Abstract
This report was prepared by Cesar Environmental Economics Consulting under awards CRI-3, 4 and 5 from the US Department of the Interior and National Oceanographic and Atmospheric Administration. The statements, findings, conclusions, and recommendations are those of the author(s) and do not necessarily reflect the views of the Department of Interior, NOAA, or the government of the CNMI.
- Published
- 2016
21. Cryopreservation and Banking of Dental Stem Cells
- Author
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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.
- Published
- 2016
22. The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental Tissue Engineering
- Author
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Ratajczak, Jessica, Bronckaers, Annelies, Dillen, Yörg, Gervois, Pascal, Vangansewinkel, Tim, Driesen, Ronald B., Wolfs, Esther, Lambrichts, Ivo, and Hilkens, Petra
- Subjects
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.
- Published
- 2016
23. 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
- Author
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Gervois, Pascal, Wolfs, Esther, Ratajczak, Jessica, Dillen, Yörg, Vangansewinkel, Tim, Hilkens, Petra, Bronckaers, Annelies, Lambrichts, Ivo, and Struys, Tom
- Subjects
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.
- Published
- 2016
24. Preconditioning of Human Dental Pulp Stem Cells with Leukocyte- and Platelet-Rich Fibrin-Derived Factors Does Not Enhance Their Neuroregenerative Effect.
- Author
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Gervois, Pascal, Ratajczak, Jessica, Wolfs, Esther, Vangansewinkel, Tim, Dillen, Yörg, Merckx, Greet, Bronckaers, Annelies, and Lambrichts, Ivo
- Subjects
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]
- Published
- 2019
- Full Text
- View/download PDF
25. Molecular Imaging of Human Embryonic Stem Cells Stably Expressing Human PET Reporter Genes After Zinc Finger Nuclease-Mediated Genome Editing.
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Wolfs, Esther, Holvoet, Bryan, Ordovas, Laura, Breuls, Natacha, Helsen, Nicky, Schönberger, Matthias, Raitano, Susanna, Struys, Tom, Vanbilloen, Bert, Casteels, Cindy, Sampaolesi, Maurilio, Van Laere, Koen, Lambrichts, Ivo, Verfaillie, Catherine M., and Deroose, Christophe M.
- Published
- 2017
- Full Text
- View/download PDF
26. The Angiogenic Potential of DPSCs and SCAPs in an In Vivo Model of Dental Pulp Regeneration.
- Author
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Hilkens, Petra, Bronckaers, Annelies, Ratajczak, Jessica, Gervois, Pascal, Wolfs, Esther, and Lambrichts, Ivo
- Subjects
REGENERATION (Biology) ,DENTAL pulp ,STEM cell treatment ,TISSUE engineering ,THREE-dimensional printing ,IMMUNOCOMPROMISED patients ,LABORATORY mice - Abstract
Adequate vascularization, a restricting factor for the survival of engineered tissues, is often promoted by the addition of stem cells or the appropriate angiogenic growth factors. In this study, human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAPs) were applied in an in vivo model of dental pulp regeneration in order to compare their regenerative potential and confirm their previously demonstrated paracrine angiogenic properties. 3D-printed hydroxyapatite scaffolds containing DPSCs and/or SCAPs were subcutaneously transplanted into immunocompromised mice. After twelve weeks, histological and ultrastructural analysis demonstrated the regeneration of vascularized pulp-like tissue as well as mineralized tissue formation in all stem cell constructs. Despite the secretion of vascular endothelial growth factor in vitro, the stem cell constructs did not display a higher vascularization rate in comparison to control conditions. Similar results were found after eight weeks, which suggests both osteogenic/odontogenic differentiation of the transplanted stem cells and the promotion of angiogenesis in this particular setting. In conclusion, this is the first study to demonstrate the successful formation of vascularized pulp-like tissue in 3D-printed scaffolds containing dental stem cells, emphasizing the promising role of this approach in dental tissue engineering. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
27. Dental Stem Cells: Their Potential in Neurogenesis and Angiogenesis.
- Author
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Bronckaers, Annelies, Wolfs, Esther, Ratajczak, Jessica, Hilkens, Petra, Gervois, Pascal, Lambrichts, Ivo, Martens, Wendy, and Struys, Tom
- Published
- 2016
- Full Text
- View/download PDF
28. Angiogenic Capacity of Periodontal Ligament Stem Cells Pretreated with Deferoxamine and/or Fibroblast Growth Factor-2.
- Author
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Ratajczak, Jessica, Hilkens, Petra, Gervois, Pascal, Wolfs, Esther, Jacobs, Reinhilde, Lambrichts, Ivo, and Bronckaers, Annelies
- Subjects
PERIODONTAL ligament ,DEFEROXAMINE ,FIBROBLAST growth factor 2 ,REGENERATIVE medicine ,PLACENTAL growth factor - Abstract
Periodontal ligament stem cells (PDLSCs) represent a good source of multipotent cells for cell-based therapies in regenerative medicine. The success rate of these treatments is severely dependent on the establishment of adequate vasculature in order to provide oxygen and nutrients to the transplanted cells. Pharmacological preconditioning of stem cells has been proposed as a promising method to augment their therapeutic efficacy. In this study, the aim was to improve the intrinsic angiogenic properties of PDLSCs by in vitro pretreatment with deferoxamine (DFX; 100μM), fibroblast growth factor-2 (FGF-2; 10ng/mL) or both substances combined. An antibody array revealed the differential expression of several proteins, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). ELISA data confirmed a 1.5 to 1.8-fold increase in VEGF for all tested conditions. Moreover, 48 hours after the removal of DFX, VEGF levels remained elevated (1.8-fold) compared to control conditions. FGF-2 and combination treatment resulted in a 5.4 to 13.1-fold increase in PlGF secretion, whereas DFX treatment had no effect. Furthermore, both PDLSCs as pretreated PDLSCs induced endothelial migration. Despite the significant elevated VEGF levels of pretreated PDLSCs, the induced endothelial migration was not higher by pretreated PDLSCs. We find that the observed induced endothelial cell motility was not dependent on VEGF, since blocking the VEGFR1-3 with Axitinib (0.5nM) did not inhibit endothelial motility towards PDLSCs. Taken together, this study provides evidence that preconditioning with DFX and/or FGF-2 significantly improves the angiogenic secretome of PDLSCs, in particular VEGF and PlGF secretion. However, our data suggest that VEGF is not the only player when it comes to influencing endothelial behavior by the PDLSCs. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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29. Optimization of Multimodal Imaging of Mesenchymal Stem Cells Using the Human Sodium Iodide Symporter for PET and Cerenkov Luminescence Imaging.
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Wolfs, Esther, Holvoet, Bryan, Gijsbers, Rik, Casteels, Cindy, Roberts, Scott J., Struys, Tom, Maris, Michael, Ibrahimi, Abdelilah, Debyser, Zeger, Van Laere, Koen, Verfaillie, Catherine M., and Deroose, Christophe M.
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- *
MESENCHYMAL stem cells , *SODIUM iodide , *POSITRON emission tomography , *LUMINESCENCE , *BIOLUMINESCENCE , *RADIONUCLIDE imaging - Abstract
Purpose: The use of stably integrated reporter gene imaging provides a manner to monitor the in vivo fate of engrafted cells over time in a non-invasive manner. Here, we optimized multimodal imaging (small-animal PET, Cerenkov luminescence imaging (CLI) and bioluminescence imaging (BLI)) of mesenchymal stem cells (MSCs), by means of the human sodium iodide symporter (hNIS) and firefly luciferase (Fluc) as reporters. Methods: First, two multicistronic lentiviral vectors (LV) were generated for multimodal imaging: BLI, 124I PET/SPECT and CLI. Expression of the imaging reporter genes was validated in vitro using 99mTcO4− radioligand uptake experiments and BLI. Uptake kinetics, specificity and tracer elution were determined as well as the effect of the transduction process on the cell's differentiation capacity. MSCs expressing the LV were injected intravenously or subcutaneously and imaged using small-animal PET, CLI and BLI. Results: The expression of both imaging reporter genes was functional and specific. An elution of 99mTcO4− from the cells was observed, with 31% retention after 3 h. After labeling cells with 124I in vitro, a significantly higher CLI signal was noted in hNIS expressing murine MSCs. Furthermore, it was possible to visualize cells injected intravenously using BLI or subcutaneously in mice, using 124I small-animal PET, CLI and BLI. Conclusions: This study identifies hNIS as a suitable reporter gene for molecular imaging with PET and CLI, as confirmed with BLI through the expression of Fluc. It supports the potential for a wider application of hNIS reporter gene imaging and future clinical applications. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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30. 18F-FDG Labeling of Mesenchymal Stem Cells and Multipotent Adult Progenitor Cells for PET Imaging: Effects on Ultrastructure and Differentiation Capacity.
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Wolfs, Esther, Struys, Tom, Notelaers, Tineke, Roberts, Scott J., Sohni, Abhishek, Bormans, Guy, Van Laere, Koen, Luyten, Frank P., Gheysens, Olivier, Lambrichts, Ivo, Verfaillie, Catherine M., and Deroose, Christophe M.
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- 2013
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31. Putting a price tag on nature - does it add value?
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WOLFS, ESTHER
- Subjects
VALUATION ,ECOLOGICAL economics ,BIODIVERSITY ,ECONOMICS - Abstract
The article discusses a study which examined the economic value of ecosystem services, biodiversity and cultural services.
- Published
- 2015
32. Selective PDE4 subtype inhibition provides new opportunities to intervene in neuroinflammatory versus myelin damaging hallmarks of multiple sclerosis
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Melissa Schepers, Dean Paes, Assia Tiane, Ben Rombaut, Elisabeth Piccart, Lieve van Veggel, Pascal Gervois, Esther Wolfs, Ivo Lambrichts, Chiara Brullo, Olga Bruno, Ernesto Fedele, Roberta Ricciarelli, Charles ffrench-Constant, Marie E. Bechler, Pauline van Schaik, Wia Baron, Evy Lefevere, Kobi Wasner, Anne Grünewald, Catherine Verfaillie, Paulien Baeten, Bieke Broux, Paul Wieringa, Niels Hellings, Jos Prickaerts, Tim Vanmierlo, Grunewald, Anne/0000-0002-4179-2994, SCHEPERS, Melissa, PAES, Dean, TIANE, Assia, ROMBAUT, Ben, PICCART, Elisabeth, VAN VEGGEL, Lieve, GERVOIS, Pascal, Brullo, Chiara, Bruno, Olga, Fedele, Ernesto, Ricciarelli, Roberta, Ffrench-Constant, Charles, Bechler, Marie E., Schaik, Pauline van, WOLFS, Esther, LAMBRICHTS, Ivo, Baron, Wia, LEFEVERE, Evy, Wasner, Kobi, Gruenewald, Anne, Verfaillie, Catherine, Wieringa, Paul, Prickaerts, Jos, BROUX, Bieke, BAETEN, Paulien, HELLINGS, Niels, VANMIERLO, Tim, RS: MHeNs - R3 - Neuroscience, Basic Neuroscience 2, Basic Neuroscience 1, CTR, RS: MERLN - Complex Tissue Regeneration (CTR), and Psychiatrie & Neuropsychologie
- Subjects
Multiple sclerosis ,Behavioral Neuroscience ,Neuroinflammation ,Remyelination ,Endocrine and Autonomic Systems ,Phosphodiesterases ,Immunology ,Biochemistry, biophysics & molecular biology [F05] [Life sciences] ,Biochimie, biophysique & biologie moléculaire [F05] [Sciences du vivant] - Abstract
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by focal inflammatory lesions and prominent demyelination. Even though the currently available therapies are effective in treating the initial stages of disease, they are unable to halt or reverse disease progression into the chronic progressive stage. Thus far, no repair-inducing treatments are available for progressive MS patients. Hence, there is an urgent need for the development of new therapeutic strategies either targeting the destructive immunological demyelination or boosting endogenous repair mechanisms. Using in vitro, ex vivo, and in vivo models, we demonstrate that selective inhibition of phosphodiesterase 4 (PDE4), a family of enzymes that hydrolyzes and inactivates cyclic adenosine monophosphate (cAMP), reduces inflammation and promotes myelin repair. More specifically, we segregated the myelination-promoting and anti-inflammatory effects into a PDE4Dand PDE4B-dependent process respectively. We show that inhibition of PDE4D boosts oligodendrocyte progenitor cells (OPC) differentiation and enhances (re)myelination of both murine OPCs and human iPSC-derived OPCs. In addition, PDE4D inhibition promotes in vivo remyelination in the cuprizone model, which is accompanied by improved spatial memory and reduced visual evoked potential latency times. We further identified that PDE4B-specific inhibition exerts anti-inflammatory effects since it lowers in vitro monocytic nitric oxide (NO) production and improves in vivo neurological scores during the early phase of experimental autoimmune encephalomyelitis (EAE). In contrast to the pan PDE4 inhibitor roflumilast, the therapeutic dose of both the PDE4B-specific inhibitor A33 and the PDE4D-specific inhibitor Gebr32a did not trigger emesis-like side effects in rodents. Finally, we report distinct PDE4D isoform expression patterns in human area postrema neurons and human oligodendroglia lineage cells. Using the CRISPR-Cas9 system, we confirmed that pde4d1/2 and pde4d6 are the key targets to induce OPC differentiation. Collectively, these data demonstrate that gene specific PDE4 inhibitors have potential as novel therapeutic agents for targeting the distinct disease processes of MS. This work has been supported by FWO (12G0817N, 1S57521N, G041421N, and 12G0817N), Fondation Charctot Stichting (ID2020- 0019), Nationale Belgische Multiple Sclerose Liga (Charco18VT), MS Liga Vlaanderen and Stichting MS Research (18-1016 MS). MS, EP, JP and TV have a proprietary interest in selective PDE4D inhibitors for the treatment of demyelinating disorders and neurodegenerative disorders. JP has a proprietary interest in the PDE4 inhibitor roflumilast for the treatment of cognitive impairment as well as PDE4D inhibitors for the treatment of Alzheimer’s disease. We thank Prof. Dr. O.N. Viacheslav (University Medical Center Hamburg-Eppendorf, German Center for Cardiovascular Research) and Prof. Dr. M. Conti (University of California), for providing the PDE4B KO animals. Furthermore, we thank Rewind Therapeutics for providing the visual evoked potential equipment.
- Published
- 2023
33. Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis
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Laura García-Mendívil, María Pérez-Zabalza, Konstantinos Mountris, Sam Duwé, Nick Smisdom, Marta Pérez, Lluís Luján, Esther Wolfs, Ronald B. Driesen, José María Vallejo-Gil, Pedro Carlos Fresneda-Roldán, Javier Fañanás-Mastral, Manuel Vázquez-Sancho, Marta Matamala-Adell, Juan Fernando Sorribas-Berjón, Javier André Bellido-Morales, Francisco Javier Mancebón-Sierra, Alexánder Sebastián Vaca-Núñez, Carlos Ballester-Cuenca, Aida Oliván-Viguera, Emiliano Diez, Laura Ordovás, Esther Pueyo, Garcia-Mendivil, Laura, Perez-Zabalza, Maria, Mountris, Konstantinos, DUWE, Sam, SMISDOM, Nick, Perez, Marta, Lujan, Lluis, WOLFS, Esther, DRIESEN, Ronald, Maria Vallejo-Gil, Jose, Carlos Fresneda-Roldan, Pedro, Fananas-Mastral, Javier, Vazquez-Sancho, Manuel, Matamala-Adell, Marta, Fernando Sorribas-Berjon, Juan, Andre Bellido-Morales, Javier, Javier Mancebon-Sierra, Francisco, Sebastian Vaca-Nunez, Alexander, Ballester-Cuenca, Carlos, Olivan-Viguera, Aida, Diez, Emiliano, Ordovas, Laura, and Pueyo, Esther
- Subjects
ARRHYTHMIAS ,Science & Technology ,Multidisciplinary ,MYOCARDIAL FIBROSIS ,IMAGES ,Science ,HEARTS ,Computational bioinformatics ,QUANTIFICATION ,Pathophysiology ,Multidisciplinary Sciences ,CONDUCTION ,LIPOFUSCIN ,Science & Technology - Other Topics ,Disease ,CARDIAC FIBROSIS ,MATRIX ,SYSTEM - Abstract
Age-related fibrosis in the left ventricle (LV) has been mainly studied in animals by assessing collagen content. Using second-harmonic generation microscopy and image processing, we evaluated amount, aggregation and spatial distribution of LV collagen in young to old pigs, and middle-age and elder living donors. All collagen features increased when comparing adult and old pigs with young ones, but not when comparing adult with old pigs or middle-age with elder individuals. Remarkably, all collagen parameters strongly correlated with lipofuscin, a biological age marker, in humans. By building patient-specific models of human ventricular tissue electrophysiology, we confirmed that amount and organization of fibrosis modulated arrhythmia vulnerability, and that distribution should be accounted for arrhythmia risk assessment. In conclusion, we characterize the age associated changes in LV collagen and its potential implications for ventricular arrhythmia development. Consistency between pig and human results substantiate the pig as a relevant model of age-related LV collagen dynamics. This work was supported by Ministerio de Ciencia e Innovacio´ n (Spain) (PID2019-105674RB-I00), by Gobierno de Arago´ n (LMP94_21) and (LMP128_21), by the European Research Council through grant ERC-StG 638284 and by European Social Fund and by Gobierno de Arago´ n (Reference Group BSICoS T39-20R) cofunded by FEDER 2014–2020 ‘‘Building Europe from Aragon‘‘. L.G-M was supported by a predoctoral fellowship from the Departamento de Ciencia, Universidad y Sociedad del Conocimiento from the Gobierno de Arago´ n 2016–2020 cofounded by Programa Operativo del Fondo Social Europeo Arago´ n (C150/2016), EMBO Short-Term fellowship (7710), and Ibercaja-CAI Estancias de Investigacio´ n IT18/18. Authors would like to acknowledge the Experimental Surgery Service of Aragon Health Sciences Institute (CIBA, Zaragoza, Spain), Mercazaragoza slaughterhouse (Zaragoza, Spain), and The Pink Pig slaughterhouse (Zuera, Spain) for their collaboration in the collection of young, adult, and boar tissue specimens, respectively.
- Published
- 2022
34. The role of lysosomal cathepsins D and B in Charcot-Marie-Tooth disease type 1A
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Dirkx, Nathalie, WOLFS, Esther, and Dirkx, Nathalie
- Published
- 2022
35. Optogenetic manipulation of dopaminergic neurons in a preclinical rodent model of Parkinson's disease
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Caz, Nuran, WOLFS, Esther, and HEUER, Andreas
- Published
- 2021
36. Gap junction intercellular communication in suicide gene therapy for oral squamous cell carcinoma: an in vitro study
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Nijsten, Kim and WOLFS, Esther
- Published
- 2021
37. Glyphosate and AMPA exposure in relation to markers of biological aging in an adult population-based study.
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Cosemans, Charlotte, Van Larebeke, Nicolas, Janssen, Bram G, Martens, Dries S, Baeyens, Willy, Bruckers, Liesbeth, Den Hond, Elly, Coertjens, Dries, Nelen, Vera, Schoeters, Greet, Hoppe, Hans-Wolfgang, Wolfs, Esther, Smeets, Karen, Nawrot, Tim S, and Plusquin, Michelle
- Subjects
- *
GLYPHOSATE , *TELOMERES , *BIOMARKERS , *MITOCHONDRIAL DNA , *MASS spectrometry , *HERBICIDES , *AGING , *RESEARCH , *GLYCINE , *ORGANOPHOSPHORUS compounds , *HETEROCYCLIC compounds , *RESEARCH methodology , *EVALUATION research , *COMPARATIVE studies - Abstract
Background/aim: Glyphosate, a broad-spectrum herbicide, and its main metabolite aminomethylphosphonic acid (AMPA) are persistent in the environment. Studies showed associations between glyphosate or AMPA exposure and several adverse cellular processes, including metabolic alterations and oxidative stress.Objective: To determine the association between glyphosate and AMPA exposure and biomarkers of biological aging.Methods: We examined glyphosate and AMPA exposure, mtDNA content and leukocyte telomere length in 181 adults, included in the third cycle of the Flemish Environment and Health Study (FLEHSIII). DNA was isolated from leukocytes and the relative mtDNA content and telomere length were determined using qPCR. Urinary glyphosate and AMPA concentrations were measured by Gas Chromatography-Tandem Mass Spectrometry (GC-MS-MS). We used multiple linear regression models to associate mtDNA content and leukocyte telomere length with glyphosate or AMPA exposure while adjusting for confounding variables.Results: A doubling in urinary AMPA concentration was associated with 5.19% (95% CI: 0.49 to 10.11; p = 0.03) longer leukocyte telomere length, while no association was observed with urinary glyphosate concentration. No association between mtDNA content and urinary glyphosate nor AMPA levels was observed.Conclusions: This study showed that AMPA exposure may be associated with telomere biology in adults. [ABSTRACT FROM AUTHOR]- Published
- 2022
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38. Human dental pulp stem cells as a potential carrier for the herpes simplex-1 virus thymidine kinase suicide gene for therapy of oral squamous cell carcinoma and characterization of the 4-nitroquinoline-1-oxide rat model
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Rasking, Leentje, WOLFS, Esther, and BRONCKAERS, Annelies
- Subjects
stomatognathic diseases - Abstract
In 2018, 2.5% of all cancers could be attributed to oral cancer. Over 90% of these oral cancers belong to the class of oral squamous cell carcinoma (OSCC), which are malignancies that originate from the oral cavity and oropharynx. The survival rates have been consistent in recent decades despite numerous advances in research and therapy. Surgical resection of the oral floor or tongue leads to complications in mastication, speech and altered aesthetics. Furthermore, radio- and chemotherapy hold a high risk of tumor recurrence and adverse effects such as xerostomia. The herpes simplex virus 1-thymidine kinase (HSV1-tk) mechanism is proposed to address these side effects. Transduction of cells with the HSV1-tk suicide gene renders the cells capable to modify ganciclovir, metabolically trapping it and leading to apoptosis. To date, lentiviral vectors are used to introduce the transgene into cancer cells; however, these vectors are a suboptimal delivery system associated with safety issues. Cellular vehicles such as human dental pulp stem cells (hDPSCs) could address these issues. Human DPSCs are a subtype of mesenchymal stem cells which are known to migrate to tumorous tissue and hence, can be an ideal candidate to carry the suicide gene to the tumor. Additionally, the mutant HSV1-sr39-tk holds a higher efficiency towards ganciclovir (GCV). Therefore, we hypothesized that therapy with HSV1-sr39-tk+ hDPSCs results in the death of OSCC cells through the bystander effect and elicits a subsequent reduction of tumor size.
- Published
- 2019
39. Advances and challenges in modeling inherited peripheral neuropathies using iPSCs.
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Van Lent J, Prior R, Pérez Siles G, Cutrupi AN, Kennerson ML, Vangansewinkel T, Wolfs E, Mukherjee-Clavin B, Nevin Z, Judge L, Conklin B, Tyynismaa H, Clark AJ, Bennett DL, Van Den Bosch L, Saporta M, and Timmerman V
- Abstract
Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids., (© 2024. The Author(s).)
- Published
- 2024
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40. 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
- Abstract
Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy caused by a 1.5 megabase tandem duplication of chromosome 17 harboring the PMP22 gene. This dose-dependent overexpression of PMP22 results in disrupted Schwann cell myelination of peripheral nerves. To get better insights into the underlying pathogenic mechanisms in CMT1A, we investigated the role of PMP22 duplication on 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 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 dose-dependently downregulated 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 signaling. 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 due to an alteration in the lipid composition, which ultimately may lead to impaired axo-glial interactions. Moreover, targeting lipid handling and metabolism could hold promise for the treatment of CMT1A patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2024
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41. Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis.
- Author
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García-Mendívil L, Pérez-Zabalza M, Mountris K, Duwé S, Smisdom N, Pérez M, Luján L, Wolfs E, Driesen RB, Vallejo-Gil JM, Fresneda-Roldán PC, Fañanás-Mastral J, Vázquez-Sancho M, Matamala-Adell M, Sorribas-Berjón JF, Bellido-Morales JA, Mancebón-Sierra FJ, Vaca-Núñez AS, Ballester-Cuenca C, Oliván-Viguera A, Diez E, Ordovás L, and Pueyo E
- Abstract
Age-related fibrosis in the left ventricle (LV) has been mainly studied in animals by assessing collagen content. Using second-harmonic generation microscopy and image processing, we evaluated amount, aggregation and spatial distribution of LV collagen in young to old pigs, and middle-age and elder living donors. All collagen features increased when comparing adult and old pigs with young ones, but not when comparing adult with old pigs or middle-age with elder individuals. Remarkably, all collagen parameters strongly correlated with lipofuscin, a biological age marker, in humans. By building patient-specific models of human ventricular tissue electrophysiology, we confirmed that amount and organization of fibrosis modulated arrhythmia vulnerability, and that distribution should be accounted for arrhythmia risk assessment. In conclusion, we characterize the age-associated changes in LV collagen and its potential implications for ventricular arrhythmia development. Consistency between pig and human results substantiate the pig as a relevant model of age-related LV collagen dynamics., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
42. By the Skin of Your Teeth: A Subcutaneous Mouse Model to Study Pulp Regeneration.
- Author
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Bronckaers A, Hilkens P, Wolfs E, and Lambrichts I
- Subjects
- Animals, Blood Vessels cytology, Blood Vessels metabolism, Dental Pulp metabolism, Dentin metabolism, Mice, Mice, Nude, Mice, SCID, Models, Animal, Skin metabolism, Stem Cells cytology, Tissue Engineering methods, Tissue Scaffolds, Dental Pulp cytology, Regeneration physiology, Skin cytology
- Abstract
Exiting developments in tissue engineering and new insights in stem cell biology have led to new possible strategies for the regeneration of damaged tissues in the oral cavity. The regeneration of the pulp-dentin complex regeneration in particular, has drawn the attention of many researchers because of the high clinical needs. While it is still important to perform in vitro research using a wide variety of cells, scaffolds and growth factors, it is also critical to have a reliable animal model for preclinical trials. In this chapter, we describe a mouse model in which a scaffold resembling a tooth containing dental pulp cells is implanted subcutaneously. We also describe which histological stainings could be used to examine blood vessel formation and the regeneration of the pulp-dentin complex.
- Published
- 2021
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43. Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain.
- Author
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Bogie JFJ, Grajchen E, Wouters E, Corrales AG, Dierckx T, Vanherle S, Mailleux J, Gervois P, Wolfs E, Dehairs J, Van Broeckhoven J, Bowman AP, Lambrichts I, Gustafsson JÅ, Remaley AT, Mulder M, Swinnen JV, Haidar M, Ellis SR, Ntambi JM, Zelcer N, and Hendriks JJA
- Subjects
- ATP Binding Cassette Transporter 1 metabolism, Animals, Cell Line, Cholesterol metabolism, Endocytosis, Fatty Acids metabolism, Foam Cells metabolism, Humans, Inflammation pathology, Macrophages metabolism, Macrophages ultrastructure, Mice, Microglia metabolism, Myelin Sheath metabolism, Phagocytes pathology, Phagocytes ultrastructure, Phenotype, Protein Kinase C-delta metabolism, Stearoyl-CoA Desaturase deficiency, Brain pathology, Macrophages enzymology, Microglia enzymology, Stearoyl-CoA Desaturase metabolism
- Abstract
Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2020 Bogie et al.)
- Published
- 2020
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44. Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha.
- Author
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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
- Full Text
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45. The human somatostatin receptor type 2 as an imaging and suicide reporter gene for pluripotent stem cell-derived therapy of myocardial infarction.
- Author
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Neyrinck K, Breuls N, Holvoet B, Oosterlinck W, Wolfs E, Vanbilloen H, Gheysens O, Duelen R, Gsell W, Lambrichts I, Himmelreich U, Verfaillie CM, Sampaolesi M, and Deroose CM
- Subjects
- Animals, Cell Line, Female, Genes, Reporter, Human Embryonic Stem Cells cytology, Human Embryonic Stem Cells metabolism, Humans, Luciferases genetics, Luciferases metabolism, Mice, Mice, Nude, Myocardial Infarction diagnostic imaging, Myocytes, Cardiac cytology, Myocytes, Cardiac metabolism, Octreotide analogs & derivatives, Organometallic Compounds, Positron-Emission Tomography, Radiopharmaceuticals, Receptors, Somatostatin genetics, Stem Cell Transplantation adverse effects, Teratoma etiology, Human Embryonic Stem Cells transplantation, Myocardial Infarction therapy, Receptors, Somatostatin metabolism, Stem Cell Transplantation methods, Teratoma diagnostic imaging
- Abstract
Rationale: Pluripotent stem cells (PSCs) are being investigated as a cell source for regenerative medicine since they provide an infinitive pool of cells that are able to differentiate towards every cell type of the body. One possible therapeutic application involves the use of these cells to treat myocardial infarction (MI), a condition where billions of cardiomyocytes (CMs) are lost. Although several protocols have been developed to differentiate PSCs towards CMs, none of these provide a completely pure population, thereby still posing a risk for neoplastic teratoma formation. Therefore, we developed a strategy to (i) monitor cell behavior noninvasively via site-specific integration of firefly luciferase (Fluc) and the human positron emission tomography (PET) imaging reporter genes, sodium iodide symporter (hNIS) and somatostatin receptor type 2 (hSSTr2), and (ii) perform hSSTr2-mediated suicide gene therapy via the clinically used radiopharmacon
177 Lu-DOTATATE. Methods: Human embryonic stem cells (ESCs) were gene-edited via zinc finger nucleases to express Fluc and either hNIS or hSSTr2 in the safe harbor locus, adeno-associated virus integration site 1. Firstly, these cells were exposed to 4.8 MBq177 Lu-DOTATATE in vitro and cell survival was monitored via bioluminescence imaging (BLI). Afterwards, hNIS+ and hSSTr2+ ESCs were transplanted subcutaneously and teratomas were allowed to form. At day 59, baseline124 I and68 Ga-DOTATATE PET and BLI scans were performed. The day after, animals received either saline or 55 MBq177 Lu-DOTATATE. Weekly BLI scans were performed, accompanied by124 I and68 Ga-DOTATATE PET scans at days 87 and 88, respectively. Finally, hSSTr2+ ESCs were differentiated towards CMs and transplanted intramyocardially in the border zone of an infarct that was induced by left anterior descending coronary artery ligation. After transplantation, the animals were monitored via BLI and PET, while global cardiac function was evaluated using cardiac magnetic resonance imaging. Results: Teratoma growth of both hNIS+ and hSSTr2+ ESCs could be followed noninvasively over time by both PET and BLI. After177 Lu-DOTATATE administration, successful cell killing of the hSSTr2+ ESCs was achieved both in vitro and in vivo , indicated by reductions in total tracer lesion uptake, BLI signal and teratoma volume. As undifferentiated hSSTr2+ ESCs are not therapeutically relevant, they were differentiated towards CMs and injected in immune-deficient mice with a MI. Long-term cell survival could be monitored without uncontrolled cell proliferation. However, no improvement in the left ventricular ejection fraction was observed. Conclusion: We developed isogenic hSSTr2-expressing ESCs that allow noninvasive cell monitoring in the context of PSC-derived regenerative therapy. Furthermore, we are the first to use the hSSTr2 not only as an imaging reporter gene, but also as a suicide mechanism for radionuclide therapy in the setting of PSC-derived cell treatment., Competing Interests: Competing interests: Katrien Neyrinck works as an aspirant for the FWO, while both Natacha Breuls and Bryan Holvoet work under an SB-grant of the FWO. Christophe M. Deroose is a consultant for Advanced Accelerator Applications (AAA) and Novartis, who hold rights to commercialize 177Lu-DOTATATE. He is also a consultant for Sirtex, Bayer, Ipsen and Terumo. He received travel grants from GE Healthcare. No other potential conflict of interest relevant to this article was reported.- Published
- 2018
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46. Efficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition.
- Author
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Ordovás L, Boon R, Pistoni M, Chen Y, Wolfs E, Guo W, Sambathkumar R, Bobis-Wozowicz S, Helsen N, Vanhove J, Berckmans P, Cai Q, Vanuytsel K, Eggermont K, Vanslembrouck V, Schmidt BZ, Raitano S, Van Den Bosch L, Nahmias Y, Cathomen T, Struys T, and Verfaillie CM
- Published
- 2018
- Full Text
- View/download PDF
47. SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells.
- Author
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García-León JA, Kumar M, Boon R, Chau D, One J, Wolfs E, Eggermont K, Berckmans P, Gunhanlar N, de Vrij F, Lendemeijer B, Pavie B, Corthout N, Kushner SA, Dávila JC, Lambrichts I, Hu WS, and Verfaillie CM
- Subjects
- Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis therapy, Antigens, Surface genetics, Gene Expression Regulation, Developmental, Humans, Multiple Sclerosis genetics, Multiple Sclerosis pathology, Multiple Sclerosis therapy, Myelin Basic Protein genetics, Neurons pathology, Neurons transplantation, Oligodendroglia cytology, Oligodendroglia transplantation, Pluripotent Stem Cells cytology, Pluripotent Stem Cells transplantation, Transcriptome genetics, Cell Differentiation genetics, Oligodendroglia metabolism, Pluripotent Stem Cells metabolism, SOXE Transcription Factors genetics
- Abstract
Scarce access to primary samples and lack of efficient protocols to generate oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering our understanding of OL biology and the development of novel therapies. Here, we demonstrate that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4
+ ) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The SOX10-induced O4+ population resembles primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OL-neuron co-cultures, myelination of neurons by OLs can also be demonstrated, which can be adapted to a high-throughput screening format to test the response of pro-myelinating drugs. In conclusion, we provide an approach to generate OLs in a very rapid and efficient manner, which can be used for disease modeling, drug discovery efforts, and potentially for therapeutic OL transplantation., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
48. 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.
- Author
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Gervois P, Wolfs E, Ratajczak J, Dillen Y, Vangansewinkel T, Hilkens P, Bronckaers A, Lambrichts I, and Struys T
- Subjects
- 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
- Full Text
- View/download PDF
49. Cryopreservation and Banking of Dental Stem Cells.
- Author
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Hilkens P, Driesen RB, Wolfs E, Gervois P, Vangansewinkel T, Ratajczak J, Dillen Y, Bronckaers A, and Lambrichts I
- Subjects
- 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
- Full Text
- View/download PDF
50. The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental Tissue Engineering.
- Author
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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
- Full Text
- View/download PDF
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