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1. Off‐the‐Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model.

Author

Besseling, Paul J., Szymczyk, Wojciech, Teraa, Martin, Toorop, Raechel J., Wu, Dan Jing, Driessen, Rob C. H., Lichauco, Arturo M., Janssen, Henk M., van de Kaa, Melanie, den Ouden, Krista, de Bree, Petra M., Fledderus, Joost O., Bouten, Carlijn V. C., de Borst, Gert J., Dankers, Patricia Y. W., and Verhaar, Marianne C.

Published
2024
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3. The effect of chronic kidney disease on tissue formation of in situ tissue-engineered vascular grafts

Author

Besseling, Paul J., primary, Krebber, Merle M., additional, Fledderus, Joost O., additional, Teraa, Martin, additional, den Ouden, Krista, additional, van de Kaa, Melanie, additional, de Bree, Petra M., additional, Serrero, Aurelie, additional, Bouten, Carlijn V. C., additional, Dankers, Patricia Y. W., additional, Cox, Martijn A. J., additional, and Verhaar, Marianne C., additional

Published
2023
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4. The effect of chronic kidney disease on tissue formation of in situ tissue-engineered vascular grafts

Author

Besseling, Paul J., Krebber, Merle M., Fledderus, Joost O., Teraa, Martin, den Ouden, Krista, van de Kaa, Melanie, de Bree, Petra M., Serrero, Aurelie, Bouten, Carlijn V.C., Dankers, Patricia Y.W., Cox, Martijn A.J., Verhaar, Marianne C., Besseling, Paul J., Krebber, Merle M., Fledderus, Joost O., Teraa, Martin, den Ouden, Krista, van de Kaa, Melanie, de Bree, Petra M., Serrero, Aurelie, Bouten, Carlijn V.C., Dankers, Patricia Y.W., Cox, Martijn A.J., and Verhaar, Marianne C.

Abstract

Vascular in situ tissue engineering encompasses a single-step approach with a wide adaptive potential and true off-the-shelf availability for vascular grafts. However, a synchronized balance between breakdown of the scaffold material and neo-tissue formation is essential. Chronic kidney disease (CKD) may influence this balance, lowering the usability of these grafts for vascular access in end-stage CKD patients on dialysis. We aimed to investigate the effects of CKD on in vivo scaffold breakdown and tissue formation in grafts made of electrospun, modular, supramolecular polycarbonate with ureido-pyrimidinone moieties (PC-UPy). We implanted PC-UPy aortic interposition grafts (n = 40) in a rat 5/6th nephrectomy model that mimics systemic conditions in human CKD patients. We studied patency, mechanical stability, extracellular matrix (ECM) components, total cellularity, vascular tissue formation, and vascular calcification in CKD and healthy rats at 2, 4, 8, and 12 weeks post-implantation. Our study shows successful in vivo application of a slow-degrading small-diameter vascular graft that supports adequate in situ vascular tissue formation. Despite systemic inflammation associated with CKD, no influence of CKD on patency (Sham: 95% vs CKD: 100%), mechanical stability, ECM formation (Sirius red +, Sham 16.5% vs CKD 25.0%-p:0.83), tissue composition, and immune cell infiltration was found. We did find a limited increase in vascular calcification at 12 weeks (Sham 0.08% vs CKD 0.80%-p:0.02) in grafts implanted in CKD animals. However, this was not associated with increased stiffness in the explants. Our findings suggest that disease-specific graft design may not be necessary for use in CKD patients on dialysis.

Published
2023

5. The effect of chronic kidney disease on tissue formation of in situ tissue-engineered vascular grafts.

Author

Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, MS Nefrologie, Zorgeenheid Vaatchirurgie Medisch, Circulatory Health, Besseling, Paul J, Krebber, Merle M, Fledderus, Joost O, Teraa, Martin, den Ouden, Krista, van de Kaa, Melanie, de Bree, Petra M, Serrero, Aurelie, Bouten, Carlijn V C, Dankers, Patricia Y W, Cox, Martijn A J, Verhaar, Marianne C, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, MS Nefrologie, Zorgeenheid Vaatchirurgie Medisch, Circulatory Health, Besseling, Paul J, Krebber, Merle M, Fledderus, Joost O, Teraa, Martin, den Ouden, Krista, van de Kaa, Melanie, de Bree, Petra M, Serrero, Aurelie, Bouten, Carlijn V C, Dankers, Patricia Y W, Cox, Martijn A J, and Verhaar, Marianne C

Published
2023

6. Early in-situ cellularization of a supramolecular vascular graft is modified by synthetic stromal cell-derived factor-1α derived peptides

Author

Muylaert, Dimitri E.P., van Almen, Geert C., Talacua, Hanna, Fledderus, Joost O., Kluin, Jolanda, Hendrikse, Simone I.S., van Dongen, Joost L.J., Sijbesma, Eline, Bosman, Anton W., Mes, Tristan, Thakkar, Shraddha H., Smits, Anthal I.P.M., Bouten, Carlijn V.C., Dankers, Patricia Y.W., and Verhaar, Marianne C.

Published
2016
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15. The in-vitro biocompatibility of ureido-pyrimidinone compounds and polymer degradation products

Author

Besseling, Paul J., Mes, Tristan, Bosman, Anton W., Peeters, Joris W., Janssen, Henk M., Bakker, Maarten H., Fledderus, Joost O., Teraa, Martin, Verhaar, Marianne C., Gremmels, Hendrik, Dankers, Patricia Y.W., Besseling, Paul J., Mes, Tristan, Bosman, Anton W., Peeters, Joris W., Janssen, Henk M., Bakker, Maarten H., Fledderus, Joost O., Teraa, Martin, Verhaar, Marianne C., Gremmels, Hendrik, and Dankers, Patricia Y.W.

Abstract

Supramolecular biomaterials based on ureido-pyrimidinone (UPy) moieties are versatile polymer materials as their function can be tailored to the application. These UPy-materials can be designed into polymer coatings, self-healing polymers, hydrogels and elastomers. The biocompatibility of UPy-based materials and their degradation products is a long-term success requirement for many regenerative medicine and biomedical applications. Earlier research has shown that UPy-based materials and polymers display no immediate toxic effects, but in-depth in-vitro studies on potential UPy-polymer degradation products have not been executed. Owing to their resemblance to naturally occurring purines and pyrimidines, UPy-compounds and their degradation products could potentially initiate an immune response or be mutagenic. Accordingly, 11 selected UPy-compounds were synthesized, and their effect on cell viability, wound healing, and their immunogenicity and potential mutagenic potential, were studied. We showed that low molecular weight degradation products of UPy-based biomaterials do not affect cell viability, nor do these interfere with several aspects of endothelial function including proliferation, angiogenic sprouting and cellular migration even in levels exceeding plausibly attainable concentrations. Furthermore, the compounds are neither immunogenic nor mutagenic, showing that UPy-biomaterials exhibit good biocompatibility in vitro, and could in principle be used in humans.

Published
2021

16. The in-vitro biocompatibility of ureido-pyrimidinone compounds and polymer degradation products

Author

Nefro Vasculaire Geneeskunde, MS Nefrologie, Regenerative Medicine and Stem Cells, Zorgeenheid Vaatchirurgie Medisch, Circulatory Health, MMB opleiding Arts microbioloog, Infection & Immunity, Besseling, Paul J., Mes, Tristan, Bosman, Anton W., Peeters, Joris W., Janssen, Henk M., Bakker, Maarten H., Fledderus, Joost O., Teraa, Martin, Verhaar, Marianne C., Gremmels, Hendrik, Dankers, Patricia Y.W., Nefro Vasculaire Geneeskunde, MS Nefrologie, Regenerative Medicine and Stem Cells, Zorgeenheid Vaatchirurgie Medisch, Circulatory Health, MMB opleiding Arts microbioloog, Infection & Immunity, Besseling, Paul J., Mes, Tristan, Bosman, Anton W., Peeters, Joris W., Janssen, Henk M., Bakker, Maarten H., Fledderus, Joost O., Teraa, Martin, Verhaar, Marianne C., Gremmels, Hendrik, and Dankers, Patricia Y.W.

Published
2021

18. SOX-18 controls endothelial-specific claudin-5 gene expression and barrier function

Author

Fontijn, Ruud D., Volger, Oscar L., Fledderus, Joost O., Reijerkerk, Arie, de Vries, Helga E., and Horrevoets, Anton J.G.

Subjects
Vascular endothelium -- Research, Epithelial cells -- Research, Cellular control mechanisms -- Research, Genetic transcription -- Research, Cardiovascular research, Biological sciences
Abstract

Members of the claudin family constitute tight junction strands and are major determinants in specificity and selectivity of paracellular barriers. Transcriptional control of clandin gene expression is essential to establish individual claudin expression patterns and barrier properties. Using full genome expression profiling, we now identify sex-determining region Y-box (SOX)-18, a member of the SOX family of high-mobility group box transcription factors, as one of the most differentially induced genes during establishment of the endothelial barrier. We show that overexpression of SOX-18 and a dominant-negative mutant thereof, as well as SOX-18 silencing, greatly affect levels of claudin-5 (CLDN5). The relevance of an evolutionary conserved SOX-binding site in the CLDN5 promoter is shown using sequential promoter deletions, as well as point mutations. Furthermore, SOX-18 silencing abrogates endothelial barrier function, as measured by electric cell-substrate impedance sensing. Thus an obligatory role for SOX-18 in the regulation of CLDN5 gene expression in an endothelial-specific and cell density-dependent manner is established, as well as a crucial, nonredundant role for specifically SOX-18 in the formation of the endothelial barrier. endothelium; claudin; promoter; sox

Published
2008

19. Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Author

Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, Other research (not in main researchprogram), MS Nefrologie, Circulatory Health, Krebber, Merle M, van Dijk, Christian G M, Vernooij, Robin W M, Brandt, Maarten M, Emter, Craig A, Rau, Christoph D, Fledderus, Joost O, Duncker, Dirk J, Verhaar, Marianne C, Cheng, Caroline, Joles, Jaap A, Nefro Vasculaire Geneeskunde, Regenerative Medicine and Stem Cells, Other research (not in main researchprogram), MS Nefrologie, Circulatory Health, Krebber, Merle M, van Dijk, Christian G M, Vernooij, Robin W M, Brandt, Maarten M, Emter, Craig A, Rau, Christoph D, Fledderus, Joost O, Duncker, Dirk J, Verhaar, Marianne C, Cheng, Caroline, and Joles, Jaap A

Published
2020

21. Galectin-2 expression is dependent on the rs7291467 polymorphism and acts as an inhibitor of arteriogenesis

Author

van der Laan, Anja M., Schirmer, Stephan H., de Vries, Margreet R., Koning, Jasper J., Volger, Oscar L., Fledderus, Joost O., Bastiaansen, Antonius J.N.M., Hollander, Maurits R., Baggen, Josefien M., Koch, Karel T., Baan, Jan, Jr, Henriques, José P., van der Schaaf, René J., Vis, Marije M., Mebius, Reina E., van der Pouw Kraan, Tineke C., Quax, Paul H., Piek, Jan J., Horrevoets, Anton J., and van Royen, Niels

Published
2012
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23. Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Author

Krebber, Merle M., primary, van Dijk, Christian G. M., additional, Vernooij, Robin W. M., additional, Brandt, Maarten M., additional, Emter, Craig A., additional, Rau, Christoph D., additional, Fledderus, Joost O., additional, Duncker, Dirk J., additional, Verhaar, Marianne C., additional, Cheng, Caroline, additional, and Joles, Jaap A., additional

Published
2020
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24. Paracrine Proangiogenic Function of Human Bone Marrow-Derived Mesenchymal Stem Cells Is Not Affected by Chronic Kidney Disease

Author

van Rhijn-Brouwer, Femke C. C., primary, van Balkom, Bas W. M., additional, Papazova, Diana A., additional, Hazenbrink, Diënty H. M., additional, Meijer, Anke J., additional, Brete, Isaac, additional, Briceno, Vidalmar, additional, van Zuilen, Arjan D., additional, Toorop, Raechel J., additional, Fledderus, Joost O., additional, Gremmels, Hendrik, additional, and Verhaar, Marianne C., additional

Published
2019
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25. Characterization of Endothelial and Smooth Muscle Cells From Different Canine Vessels

Author

Oosterhoff, Loes A, Kruitwagen, Hedwig S, van Wolferen, Monique E, van Balkom, Bas W M, Mokry, Michal, Lansu, Nico, van den Dungen, Noortje A M, Penning, Louis C, Spanjersberg, Talitha C F, de Graaf, Johannes W, Veenendaal, Tomas, Zomerdijk, Flin, Fledderus, Joost O, Spee, Bart, van Steenbeek, Frank G, Biochemisch laboratorium, dCSCA RMSC-1, LS Interne geneeskunde, Sub Biomol.Mass Spect. and Proteomics, dCSCA AVR, Onderzoek, Undergraduate School, Biochemisch laboratorium, dCSCA RMSC-1, LS Interne geneeskunde, Sub Biomol.Mass Spect. and Proteomics, dCSCA AVR, Onderzoek, and Undergraduate School

Subjects
0301 basic medicine, Cell type, Vascular smooth muscle, Endothelium, Physiology, Angiogenesis, Biology, lcsh:Physiology, Transcriptome, 03 medical and health sciences, angiogenesis, 0302 clinical medicine, Tissue engineering, cell model system, vascular cell interaction, Physiology (medical), medicine, vascular smooth muscle cells, vascular smooth, Tissue homeostasis, Original Research, lcsh:QP1-981, Vascular disease, medicine.disease, endothelial cells, Cell biology, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, cardiovascular system
Abstract

Vasculature performs a critical function in tissue homeostasis, supply of oxygen and nutrients, and the removal of metabolic waste products. Vascular problems are implicated in a large variety of pathologies and accurate in vitro models resembling native vasculature are of great importance. Unfortunately, existing in vitro models do not sufficiently reflect their in vivo counterpart. The complexity of vasculature requires the examination of multiple cell types including endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), as well as vessel location in the body from which they originate. The use of canine blood vessels provides a way to study vasculature with similar vessel size and physiology compared to human vasculature. We report an isolation procedure that provides the possibility to isolate both the endothelial and smooth muscle cells from the same vessels simultaneously, enabling new opportunities in investigating vasculature behavior. Canine primary ECs and VSMCs were isolated from the vena cava, vena porta and aorta. All tissue sources were derived from three donors for accurate comparison and to reduce inter-animal variation. The isolation and purification of the two distinct cell types was confirmed by morphology, gene- and protein-expression and function. As both cell types can be derived from the same vessel, this approach allows accurate modeling of vascular diseases and can also be used more widely, for example, in vascular bioreactors and tissue engineering designs. Additionally, we identified several new genes that were highly expressed in canine ECs, which may become candidate genes for novel EC markers. In addition, we observed transcriptional and functional differences between arterial- and venous-derived endothelium. Further exploration of the transcriptome and physiology of arteriovenous differentiation of primary cells may have important implications for a better understanding of the fundamental behavior of the vasculature and pathogenesis of vascular disease.

Published
2019

26. Paracrine Proangiogenic Function of Human Bone Marrow-Derived Mesenchymal Stem Cells Is Not Affected by Chronic Kidney Disease

Author

van Rhijn-Brouwer, Femke C C, van Balkom, Bas W M, Papazova, Diana A, Hazenbrink, Diënty H M, Meijer, Anke J, Brete, Isaac, Briceno, Vidalmar, van Zuilen, Arjan D, Toorop, Raechel J, Fledderus, Joost O, Gremmels, Hendrik, Verhaar, Marianne C, van Rhijn-Brouwer, Femke C C, van Balkom, Bas W M, Papazova, Diana A, Hazenbrink, Diënty H M, Meijer, Anke J, Brete, Isaac, Briceno, Vidalmar, van Zuilen, Arjan D, Toorop, Raechel J, Fledderus, Joost O, Gremmels, Hendrik, and Verhaar, Marianne C

Published
2019

27. Characterization of Endothelial and Smooth Muscle Cells From Different Canine Vessels

Author

Biochemisch laboratorium, dCSCA RMSC-1, LS Interne geneeskunde, Sub Biomol.Mass Spect. and Proteomics, dCSCA AVR, Onderzoek, Undergraduate School, Oosterhoff, Loes A, Kruitwagen, Hedwig S, van Wolferen, Monique E, van Balkom, Bas W M, Mokry, Michal, Lansu, Nico, van den Dungen, Noortje A M, Penning, Louis C, Spanjersberg, Talitha C F, de Graaf, Johannes W, Veenendaal, Tomas, Zomerdijk, Flin, Fledderus, Joost O, Spee, Bart, van Steenbeek, Frank G, Biochemisch laboratorium, dCSCA RMSC-1, LS Interne geneeskunde, Sub Biomol.Mass Spect. and Proteomics, dCSCA AVR, Onderzoek, Undergraduate School, Oosterhoff, Loes A, Kruitwagen, Hedwig S, van Wolferen, Monique E, van Balkom, Bas W M, Mokry, Michal, Lansu, Nico, van den Dungen, Noortje A M, Penning, Louis C, Spanjersberg, Talitha C F, de Graaf, Johannes W, Veenendaal, Tomas, Zomerdijk, Flin, Fledderus, Joost O, Spee, Bart, and van Steenbeek, Frank G

Published
2019

28. Paracrine Proangiogenic Function of Human Bone Marrow-Derived Mesenchymal Stem Cells Is Not Affected by Chronic Kidney Disease

Author

Nefro Vasculaire Geneeskunde, Circulatory Health, MS Nefrologie, AIOS Anesthesiologie, Regenerative Medicine and Stem Cells, MMB opleiding Arts microbioloog, MMB Staf diagnostiek, van Rhijn-Brouwer, Femke C C, van Balkom, Bas W M, Papazova, Diana A, Hazenbrink, Diënty H M, Meijer, Anke J, Brete, Isaac, Briceno, Vidalmar, van Zuilen, Arjan D, Toorop, Raechel J, Fledderus, Joost O, Gremmels, Hendrik, Verhaar, Marianne C, Nefro Vasculaire Geneeskunde, Circulatory Health, MS Nefrologie, AIOS Anesthesiologie, Regenerative Medicine and Stem Cells, MMB opleiding Arts microbioloog, MMB Staf diagnostiek, van Rhijn-Brouwer, Femke C C, van Balkom, Bas W M, Papazova, Diana A, Hazenbrink, Diënty H M, Meijer, Anke J, Brete, Isaac, Briceno, Vidalmar, van Zuilen, Arjan D, Toorop, Raechel J, Fledderus, Joost O, Gremmels, Hendrik, and Verhaar, Marianne C

Published
2019

29. Characterization of endothelial and smooth muscle cells from different canine vessels

Author

UMC Utrecht, MS Nefrologie, Circulatory Health, Dagcentrum, Child Health, MDL onderzoek 1, Regenerative Medicine and Stem Cells, Oosterhoff, Loes A., Kruitwagen, Hedwig S., Van Wolferen, Monique E., Van Balkom, Bas W.M., Mokry, Michal, Lansu, Nico, Lansu, NR, Van Den Dungen, Noortje A.M., Penning, Louis C., Spanjersberg, Talitha C.F., De Graaf, Johannes W., Veenendaal, Tomas, Zomerdijk, Flin, Fledderus, Joost O., Spee, Bart, Van Steenbeek, Frank G., UMC Utrecht, MS Nefrologie, Circulatory Health, Dagcentrum, Child Health, MDL onderzoek 1, Regenerative Medicine and Stem Cells, Oosterhoff, Loes A., Kruitwagen, Hedwig S., Van Wolferen, Monique E., Van Balkom, Bas W.M., Mokry, Michal, Lansu, Nico, Lansu, NR, Van Den Dungen, Noortje A.M., Penning, Louis C., Spanjersberg, Talitha C.F., De Graaf, Johannes W., Veenendaal, Tomas, Zomerdijk, Flin, Fledderus, Joost O., Spee, Bart, and Van Steenbeek, Frank G.

Published
2019

30. A randomised placebo-controlled double-blind trial to assess the safety of intramuscular administration of allogeneic mesenchymal stromal cells for digital ulcers in systemic sclerosis : the MANUS Trial protocol

Author

van Rhijn-Brouwer, Femke C C, Gremmels, Hendrik, Fledderus, Joost O, Schuurman, Arnold H, Bonte-Mineur, Femke, Vonk, Madelon C, Voskuyl, Alexandre E, de Vries-Bouwstra, Jeska K, Coert, J Henk, Radstake, Timothy R D J, van Laar, Jacob M, Verhaar, Marianne C, and MANUS Study Group

Subjects
angiogenesis, systemic sclerosis, digital ulcers, mesenchymal stromal cells
Abstract

INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disease characterised by inflammation, fibrosis and vasculopathy. Digital ulcers (DUs) are a frequent manifestation of vasculopathy in patients with SSc. Despite recent advances in pharmacological treatments, DU still have major health and economic implications. As there is currently no proven therapeutic strategy to promote DU healing, new treatments are urgently needed. Mesenchymal stem or stromal cells (MSCs) may provide a novel therapy for DU in SSc, because of their immunomodulatory and vasculoregenerative properties. Allogeneic MSC therapy involves functionally competent MSCs from healthy donors and may be used as 'off-the-shelf' available treatment. This study will evaluate whether allogeneic MSC therapy is a safe and potentially efficacious treatment for DU of SSc. METHODS AND ANALYSIS: The MANUS (Mesenchymal stromal cells for Angiogenesis and Neovascularization in digital Ulcers of Systemic Sclerosis) Trial is a double-blind randomised placebo-controlled trial. 20 patients with SSc with refractory DU will be randomised to receive eight intramuscular injections with either placebo or 50*106 MSCs. The primary outcome is the toxicity of the treatment at 12 weeks after administration. Secondary outcomes include (serious) adverse events, number and time to healing of DU, pain, reported hand function, quality of life and SSc disease activity. We will also evaluate changes in nailfold capillaroscopy pattern, as well as biochemical parameters and biomarkers in peripheral blood and skin biopsies. Follow-up visits will be scheduled at 48 hours and 2, 4, 8, 12, 24 and 52 weeks post-treatment. If the results confirm safety, feasibility and potential efficacy, a large multicentre randomised controlled trial with longer follow-up will be initiated focusing on efficacy. ETHICS AND DISSEMINATION: The study has been approved by the Dutch Central Committee on Research Concerning Human Subjects (protocol no: NL51705.000.15). The results will be disseminated through patient associations and conventional scientific channels. TRIAL REGISTRATION NUMBER: NCT03211793; Pre-results.

Published
2018

31. Effect of donor variation on osteogenesis and vasculogenesis in hydrogel cocultures

Author

Pennings, Iris, primary, Dijk, Lukas A., additional, Huuksloot, Juliet, additional, Fledderus, Joost O., additional, Schepers, Koen, additional, Braat, A. Koen, additional, Hsiao, Edward C., additional, Barruet, Emilie, additional, Morales, Blanca M., additional, Verhaar, Marianne C., additional, Rosenberg, Antoine J.W.P., additional, and Gawlitta, Debby, additional

Published
2019
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32. Expression of a retinoic acid signature in circulating CD34 cells from coronary artery disease patients

Author

van der Laan Anja M, Leyen Thomas A, Baggen Josefien M, Moerland Perry D, Fledderus Joost O, Schirmer Stephan H, van der Pouw Kraan Tineke CTM, Piek Jan J, van Royen Niels, and Horrevoets Anton JG

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Circulating CD34+ progenitor cells have the potential to differentiate into a variety of cells, including endothelial cells. Knowledge is still scarce about the transcriptional programs used by CD34+ cells from peripheral blood, and how these are affected in coronary artery disease (CAD) patients. Results We performed a whole genome transcriptome analysis of CD34+ cells, CD4+ T cells, CD14+ monocytes, and macrophages from 12 patients with CAD and 11 matched controls. CD34+ cells, compared to other mononuclear cells from the same individuals, showed high levels of KRAB box transcription factors, known to be involved in gene silencing. This correlated with high expression levels in CD34+ cells for the progenitor markers HOXA5 and HOXA9, which are known to control expression of KRAB factor genes. The comparison of expression profiles of CD34+ cells from CAD patients and controls revealed a less naïve phenotype in patients' CD34+ cells, with increased expression of genes from the Mitogen Activated Kinase network and a lowered expression of a panel of histone genes, reaching levels comparable to that in more differentiated circulating cells. Furthermore, we observed a reduced expression of several genes involved in CXCR4-signaling and migration to SDF1/CXCL12. Conclusions The altered gene expression profile of CD34+ cells in CAD patients was related to activation/differentiation by a retinoic acid-induced differentiation program. These results suggest that circulating CD34+ cells in CAD patients are programmed by retinoic acid, leading to a reduced capacity to migrate to ischemic tissues.

Published
2010
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33. Folic acid supplementation normalizes the endothelial progenitor cell transcriptome of patients with type 1 diabetes: a case-control pilot study

Author

Stubbs Andrew, Pescatori Mario, Fledderus Joost O, de Kleijn Dominique PV, van Oostrom Olivia, Tuinenburg Attie, Lim Sai Kiang, and Verhaar Marianne C

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Endothelial progenitor cells play an important role in vascular wall repair. Patients with type 1 diabetes have reduced levels of endothelial progenitor cells of which their functional capacity is impaired. Reduced nitric oxide bioavailability and increased oxidative stress play a role in endothelial progenitor cell dysfunction in these patients. Folic acid, a B-vitamin with anti-oxidant properties, may be able to improve endothelial progenitor cell function. In this study, we investigated the gene expression profiles of endothelial progenitor cells from patients with type 1 diabetes compared to endothelial progenitor cells from healthy subjects. Furthermore, we studied the effect of folic acid on gene expression profiles of endothelial progenitor cells from patients with type 1 diabetes. Methods We used microarray analysis to investigate the gene expression profiles of endothelial progenitor cells from type 1 diabetes patients before (n = 11) and after a four week period of folic acid supplementation (n = 10) compared to the gene expression profiles of endothelial progenitor cells from healthy subjects (n = 11). The probability of genes being differentially expressed among the classes was computed using a random-variance t-test. A multivariate permutation test was used to identify genes that were differentially expressed among the two classes. Functional classification of differentially expressed genes was performed using the biological process ontology in the Gene Ontology database. Results Type 1 diabetes significantly modulated the expression of 1591 genes compared to healthy controls. These genes were found to be involved in processes regulating development, cell communication, cell adhesion and localization. After folic acid treatment, endothelial progenitor cell gene expression profiles from diabetic patients were similar to those from healthy controls. Genes that were normalized by folic acid played a prominent role in development, such as the transcription factors ID1 and MAFF. Few oxidative-stress related genes were affected by folic acid. Conclusion Folic acid normalizes endothelial progenitor cell gene expression profiles of patients with type 1 diabetes. Signaling pathways modulated by folic acid may be potential therapeutic targets to improve endothelial progenitor cell function.

Published
2009
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34. A randomised placebo-controlled double-blind trial to assess the safety of intramuscular administration of allogeneic mesenchymal stromal cells for digital ulcers in systemic sclerosis: the MANUS Trial protocol

Author

Nefro Vasculaire Geneeskunde, Circulatory Health, MMB Staf diagnostiek, Regenerative Medicine and Stem Cells, MS Nefrologie, Zorgeenheid Plastische Chirurgie Medisch, Other research (not in main researchprogram), Brain, Translationele immunologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, van Rhijn-Brouwer, Femke C C, Gremmels, Hendrik, Fledderus, Joost O, Schuurman, Arnold H, Bonte-Mineur, Femke, Vonk, Madelon C, Voskuyl, Alexandre E, de Vries-Bouwstra, Jeska K, Coert, J Henk, Radstake, Timothy R D J, van Laar, Jacob M, Verhaar, Marianne C, MANUS Study Group, Nefro Vasculaire Geneeskunde, Circulatory Health, MMB Staf diagnostiek, Regenerative Medicine and Stem Cells, MS Nefrologie, Zorgeenheid Plastische Chirurgie Medisch, Other research (not in main researchprogram), Brain, Translationele immunologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, van Rhijn-Brouwer, Femke C C, Gremmels, Hendrik, Fledderus, Joost O, Schuurman, Arnold H, Bonte-Mineur, Femke, Vonk, Madelon C, Voskuyl, Alexandre E, de Vries-Bouwstra, Jeska K, Coert, J Henk, Radstake, Timothy R D J, van Laar, Jacob M, Verhaar, Marianne C, and MANUS Study Group

Published
2018

35. A randomised placebo-controlled double-blind trial to assess the safety of intramuscular administration of allogeneic mesenchymal stromal cells for digital ulcers in systemic sclerosis: the MANUS Trial protocol

Author

van Rhijn-Brouwer, Femke C C, primary, Gremmels, Hendrik, additional, Fledderus, Joost O, additional, Schuurman, Arnold H, additional, Bonte-Mineur, Femke, additional, Vonk, Madelon C, additional, Voskuyl, Alexandre E, additional, de Vries-Bouwstra, Jeska K, additional, Coert, J Henk, additional, Radstake, Timothy R D J, additional, van Laar, Jacob M, additional, and Verhaar, Marianne C, additional

Published
2018
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38. The Transcription Factor Nrf2 Protects Angiogenic Capacity of Endothelial Colony-Forming Cells in High-Oxygen Radical Stress Conditions

Author

MS Nefrologie, Regenerative Medicine and Stem Cells, Medische Fysiologie, CDL Nanomedicine, Nefro Vasculaire Geneeskunde, Circulatory Health, Gremmels, Hendrik, De Jong, Olivier G., Hazenbrink, Diënty H., Fledderus, Joost O., Verhaar, Marianne C., MS Nefrologie, Regenerative Medicine and Stem Cells, Medische Fysiologie, CDL Nanomedicine, Nefro Vasculaire Geneeskunde, Circulatory Health, Gremmels, Hendrik, De Jong, Olivier G., Hazenbrink, Diënty H., Fledderus, Joost O., and Verhaar, Marianne C.

Published
2017

40. Early in-situ cellularization of a supramolecular vascular graft is modified by synthetic stromal cell-derived factor-1α derived peptides

Author

Muylaert, Dimitri E P, van Almen, Geert C, Talacua, Hanna, Fledderus, Joost O, Kluin, Jolanda, Hendrikse, Simone I S, van Dongen, Joost L J, Sijbesma, Eline, Bosman, Anton W, Mes, Tristan, Thakkar, Shraddha H, Smits, Anthal I P M, Bouten, Carlijn V C, Dankers, Patricia Y W, Verhaar, Marianne C, Muylaert, Dimitri E P, van Almen, Geert C, Talacua, Hanna, Fledderus, Joost O, Kluin, Jolanda, Hendrikse, Simone I S, van Dongen, Joost L J, Sijbesma, Eline, Bosman, Anton W, Mes, Tristan, Thakkar, Shraddha H, Smits, Anthal I P M, Bouten, Carlijn V C, Dankers, Patricia Y W, and Verhaar, Marianne C

Published
2016

41. Cellular Therapies in Systemic Sclerosis : Recent Progress

Author

van Rhijn-Brouwer, Femke C C, Gremmels, Hendrik, Fledderus, Joost O, Radstake, Timothy R D, Verhaar, Marianne C, van Laar, Jacob M, van Rhijn-Brouwer, Femke C C, Gremmels, Hendrik, Fledderus, Joost O, Radstake, Timothy R D, Verhaar, Marianne C, and van Laar, Jacob M

Published
2016

42. Lymphatic Vascular Regeneration : The Next Step in Tissue Engineering

Author

Huethorst, Eline, Krebber, Merle M, Fledderus, Joost O, Gremmels, Hendrik, Xu, Yan Juan, Pei, Jiayi, Verhaar, Marianne C, Cheng, Caroline, Huethorst, Eline, Krebber, Merle M, Fledderus, Joost O, Gremmels, Hendrik, Xu, Yan Juan, Pei, Jiayi, Verhaar, Marianne C, and Cheng, Caroline

Published
2016

44. Cellular Therapies in Systemic Sclerosis: Recent Progress

Author

Nefro Vasculaire Geneeskunde, MS Nefrologie, Translationele immunologie, Infection & Immunity, Circulatory Health, Regenerative Medicine and Stem Cells, MS Reumatologie/Immunologie/Infectie, van Rhijn-Brouwer, Femke C C, Gremmels, Hendrik, Fledderus, Joost O, Radstake, Timothy R D, Verhaar, Marianne C, van Laar, Jacob M, Nefro Vasculaire Geneeskunde, MS Nefrologie, Translationele immunologie, Infection & Immunity, Circulatory Health, Regenerative Medicine and Stem Cells, MS Reumatologie/Immunologie/Infectie, van Rhijn-Brouwer, Femke C C, Gremmels, Hendrik, Fledderus, Joost O, Radstake, Timothy R D, Verhaar, Marianne C, and van Laar, Jacob M

Published
2016

45. Environmental Influences on Endothelial to Mesenchymal Transition in Developing Implanted Cardiovascular Tissue-Engineered Grafts

Author

Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, MS Nefrologie, Muylaert, Dimitri E P, de Jong, Olivier G, Slaats, Gisela G G, Nieuweboer, Frederieke E, Fledderus, Joost O, Goumans, Marie-Jose, Hierck, Beerend P, Verhaar, Marianne C, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, MS Nefrologie, Muylaert, Dimitri E P, de Jong, Olivier G, Slaats, Gisela G G, Nieuweboer, Frederieke E, Fledderus, Joost O, Goumans, Marie-Jose, Hierck, Beerend P, and Verhaar, Marianne C

Published
2016

46. Lymphatic Vascular Regeneration: The Next Step in Tissue Engineering

Author

Nefro Vasculaire Geneeskunde, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, Huethorst, Eline, Krebber, Merle M, Fledderus, Joost O, Gremmels, Hendrik, Xu, Yan Juan, Pei, Jiayi, Verhaar, Marianne C, Cheng, Caroline, Nefro Vasculaire Geneeskunde, MS Nefrologie, Regenerative Medicine and Stem Cells, Circulatory Health, Huethorst, Eline, Krebber, Merle M, Fledderus, Joost O, Gremmels, Hendrik, Xu, Yan Juan, Pei, Jiayi, Verhaar, Marianne C, and Cheng, Caroline

Published
2016

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