8 results on '"Breuls N"'
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2. Diastolic-systolic coronary flow differences are caused by intramyocardial pump action in the anesthetized dog.
- Author
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Spaan, J A, primary, Breuls, N P, additional, and Laird, J D, additional
- Published
- 1981
- Full Text
- View/download PDF
3. Valproic acid stimulates myogenesis in pluripotent stem cell-derived mesodermal progenitors in a NOTCH-dependent manner.
- Author
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Breuls N, Giarratana N, Yedigaryan L, Garrido GM, Carai P, Heymans S, Ranga A, Deroose C, and Sampaolesi M
- Subjects
- Animals, Cell Lineage, Cells, Cultured, Coculture Techniques, Disease Models, Animal, Female, Humans, Induced Pluripotent Stem Cells metabolism, Induced Pluripotent Stem Cells transplantation, Male, Mesoderm cytology, Mesoderm metabolism, Mesoderm transplantation, Mice, Mice, Knockout, Muscle Contraction, Muscle Fibers, Skeletal metabolism, Muscle Fibers, Skeletal transplantation, Muscle Strength, Muscle, Skeletal metabolism, Muscle, Skeletal physiopathology, Muscular Dystrophies genetics, Muscular Dystrophies metabolism, Muscular Dystrophies physiopathology, Muscular Dystrophies surgery, Myocytes, Cardiac metabolism, Myocytes, Cardiac transplantation, Phenotype, Rats, Signal Transduction, Cell Differentiation drug effects, Induced Pluripotent Stem Cells drug effects, Mesoderm drug effects, Muscle Development drug effects, Muscle Fibers, Skeletal drug effects, Myocytes, Cardiac drug effects, Receptors, Notch metabolism, Valproic Acid pharmacology
- Abstract
Muscular dystrophies are debilitating neuromuscular disorders for which no cure exists. As this disorder affects both cardiac and skeletal muscle, patients would benefit from a cellular therapy that can simultaneously regenerate both tissues. The current protocol to derive bipotent mesodermal progenitors which can differentiate into cardiac and skeletal muscle relies on the spontaneous formation of embryoid bodies, thereby hampering further clinical translation. Additionally, as skeletal muscle is the largest organ in the human body, a high myogenic potential is necessary for successful regeneration. Here, we have optimized a protocol to generate chemically defined human induced pluripotent stem cell-derived mesodermal progenitors (cdMiPs). We demonstrate that these cells contribute to myotube formation and differentiate into cardiomyocytes, both in vitro and in vivo. Furthermore, the addition of valproic acid, a clinically approved small molecule, increases the potential of the cdMiPs to contribute to myotube formation that can be prevented by NOTCH signaling inhibitors. Moreover, valproic acid pre-treated cdMiPs injected in dystrophic muscles increase physical strength and ameliorate the functional performances of transplanted mice. Taken together, these results constitute a novel approach to generate mesodermal progenitors with enhanced myogenic potential using clinically approved reagents.
- Published
- 2021
- Full Text
- View/download PDF
4. Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles.
- Author
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Camps J, Breuls N, Sifrim A, Giarratana N, Corvelyn M, Danti L, Grosemans H, Vanuytven S, Thiry I, Belicchi M, Meregalli M, Platko K, MacDonald ME, Austin RC, Gijsbers R, Cossu G, Torrente Y, Voet T, and Sampaolesi M
- Subjects
- Animals, Fibrosis metabolism, Fibrosis pathology, Humans, Male, Mice, Muscle, Skeletal metabolism, Muscular Dystrophy, Duchenne metabolism, Adipogenesis physiology, Cell Differentiation physiology, Leydig Cells cytology, Muscle, Skeletal pathology, Muscular Dystrophy, Duchenne pathology
- Abstract
Fibrosis and fat replacement in skeletal muscle are major complications that lead to a loss of mobility in chronic muscle disorders, such as muscular dystrophy. However, the in vivo properties of adipogenic stem and precursor cells remain unclear, mainly due to the high cell heterogeneity in skeletal muscles. Here, we use single-cell RNA sequencing to decomplexify interstitial cell populations in healthy and dystrophic skeletal muscles. We identify an interstitial CD142-positive cell population in mice and humans that is responsible for the inhibition of adipogenesis through GDF10 secretion. Furthermore, we show that the interstitial cell composition is completely altered in muscular dystrophy, with a near absence of CD142-positive cells. The identification of these adipo-regulatory cells in the skeletal muscle aids our understanding of the aberrant fat deposition in muscular dystrophy, paving the way for treatments that could counteract degeneration in patients with muscular dystrophy., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
5. (Epi)genetic Modifications in Myogenic Stem Cells: From Novel Insights to Therapeutic Perspectives.
- Author
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Breuls N, Giacomazzi G, and Sampaolesi M
- Subjects
- Cell Differentiation genetics, Humans, Models, Biological, Mutation genetics, Epigenesis, Genetic, Muscle Development genetics, Stem Cells metabolism
- Abstract
The skeletal muscle is considered to be an ideal target for stem cell therapy as it has an inherent regenerative capacity. Upon injury, the satellite cells, muscle stem cells that reside under the basal lamina of the myofibres, start to differentiate in order to reconstitute the myofibres while maintaining the initial stem cell pool. In recent years, it has become more and more evident that epigenetic mechanisms such as histon modifications, DNA methylations and microRNA modulations play a pivatol role in this differentiation process. By understanding the mechanisms behind myogenesis, researchers are able to use this knowledge to enhance the differentiation and engraftment potential of different muscle stem cells. Besides manipulation on an epigenetic level, recent advances in the field of genome-engineering allow site-specific modifications in the genome of these stem cells. Combining epigenetic control of the stem cell fate with the ability to site-specifically correct mutations or add genes for further cell control, can increase the use of stem cells as treatment of muscular dystrophies drastically. In this review, we will discuss the advances that have been made in genome-engineering and the epigenetic regulation of muscle stem cells and how this knowledge can help to get stem cell therapy to its full potential.
- Published
- 2019
- Full Text
- View/download PDF
6. 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
- Full Text
- View/download PDF
7. Molecular Imaging of Human Embryonic Stem Cells Stably Expressing Human PET Reporter Genes After Zinc Finger Nuclease-Mediated Genome Editing.
- Author
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Wolfs E, Holvoet B, Ordovas L, Breuls N, Helsen N, Schönberger M, Raitano S, Struys T, Vanbilloen B, Casteels C, Sampaolesi M, Van Laere K, Lambrichts I, Verfaillie CM, and Deroose CM
- Subjects
- Animals, Cell Differentiation, Cell Line, Endoribonucleases chemistry, Female, Gene Expression, Humans, Liver cytology, Mice, Embryonic Stem Cells metabolism, Endoribonucleases metabolism, Gene Editing, Genes, Reporter genetics, Genome, Human genetics, Positron-Emission Tomography, Zinc Fingers
- Abstract
Molecular imaging is indispensable for determining the fate and persistence of engrafted stem cells. Standard strategies for transgene induction involve the use of viral vectors prone to silencing and insertional mutagenesis or the use of nonhuman genes. Methods: We used zinc finger nucleases to induce stable expression of human imaging reporter genes into the safe-harbor locus adeno-associated virus integration site 1 in human embryonic stem cells. Plasmids were generated carrying reporter genes for fluorescence, bioluminescence imaging, and human PET reporter genes. Results: In vitro assays confirmed their functionality, and embryonic stem cells retained differentiation capacity. Teratoma formation assays were performed, and tumors were imaged over time with PET and bioluminescence imaging. Conclusion: This study demonstrates the application of genome editing for targeted integration of human imaging reporter genes in human embryonic stem cells for long-term molecular imaging., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)
- Published
- 2017
- Full Text
- View/download PDF
8. LV lead fixation in a coronary vein may be the cause and result of thrombosis.
- Author
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Breuls N and Res JC
- Subjects
- Aged, Female, Humans, Coronary Vessels injuries, Electrodes, Implanted adverse effects, Heart Ventricles surgery, Pacemaker, Artificial adverse effects, Veins injuries, Venous Thrombosis diagnosis, Venous Thrombosis etiology
- Abstract
A recently implanted left ventricular lead was fixated in the coronary sinus due to thrombosis while attempting to reposition the lead because of phrenic nerve stimulation.
- Published
- 2008
- Full Text
- View/download PDF
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