A5069681325- Cancer-related molecular mechanisms research
- Proteoglycans and glycosaminoglycans research
- Congenital heart defects research
- Mesenchymal stem cell research
- MicroRNA in disease regulation
- Tissue Engineering and Regenerative Medicine
- Protease and Inhibitor Mechanisms
- Chronic Lymphocytic Leukemia Research
- Blood Coagulation and Thrombosis Mechanisms
- Glycosylation and Glycoproteins Research
- Atherosclerosis and Cardiovascular Diseases
- Cardiac Valve Diseases and Treatments
- Circular RNAs in diseases
- Cerebrovascular and Carotid Artery Diseases
- Fibroblast Growth Factor Research
- Pancreatic and Hepatic Oncology Research
- Pancreatic function and diabetes
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Connective tissue disorders research
- Immunodeficiency and Autoimmune Disorders
- Aortic Disease and Treatment Approaches
- Autophagy in Disease and Therapy
- T-cell and B-cell Immunology
- Cardiac Fibrosis and Remodeling
Karolinska Institutet
2015-2024
Karolinska University Hospital
2007-2019
Nova Southeastern University
2016-2018
Kyung Hee University
2018
Universität Hamburg
2016
University Medical Center Hamburg-Eppendorf
2016
Stanford University
2016
Maria Cecilia Hospital
2013-2016
Novo Nordisk (Denmark)
2013
Stockholm South General Hospital
2013
In the search for markers and modulators of vascular disease, microRNAs (miRNAs) have emerged as potent therapeutic targets.To investigate miRNAs clinical interest in patients with unstable carotid stenosis at risk stroke.Using patient material from BiKE (Biobank Karolinska Endarterectomies), we profiled miRNA expression stable versus plaque. A polymerase chain reaction-based array plasma, sampled lesion site, identified 8 deregulated (miR-15b, miR-29c, miR-30c/d, miR-150, miR-191, miR-210,...
Objective— Carotid plaque instability is a major cause of ischemic stroke, but detailed knowledge about underlying molecular pathways still lacking. Here, we evaluated large-scale transcriptomic and protein expression profiling in biobank carotid endarterectomies followed by characterization identified candidates, as platform for discovery novel proteins differentially regulated unstable lesions. Approach Results— Genes highly upregulated symptomatic versus asymptomatic plaques were selected...
Abstract Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond currently established genomic transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize transcriptome alongside genetic ex-vivo drug profiling a annotated CLL discovery cohort (n = 68). Unsupervised clustering data reveals six...
// Hao Cui 1,* , Ying-xia Tan 1,2,* Cecilia Österholm 3,4 Xiao Zhang 5 Ulf Hedin 3 Israel Vlodavsky 6 and Jin-Ping Li 1 Department of Medical Biochemistry Microbiology, SciLifeLab Uppsala, The Biomedical Center, University Husargatan, Sweden 2 Tissue Engineering, Beijing Institute Transfusion Medicine, Beijing, China Molecular Medicine Surgery, Karolinska Institutet, Stockholm, 4 Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, FL, USA Neuroscience Pharmacology, Cancer...
Abstract Disturbed flow has been suggested to contribute aneurysm susceptibility in bicuspid aortic valve (BAV) patients. Lately, emerged as an important modulator of DNA methylation. Hear we combined global methylation analysis with vitro studies flow-sensitive identify biological processes associated BAV-aortopathy and the potential contribution flow. Biopsies from non-dilated dilated ascending aortas were collected BAV (n = 21) tricuspid (TAV) patients 23). gene expression was measured...
Heparan sulfate (HS) chains bind and modulate the signaling efficiency of many ligands, including members fibroblast growth factor (FGF) platelet-derived families. We previously reported structure HS synthesized by embryonic fibroblasts from mice with a gene trap mutation Ext1 that encodes glycosyltransferase involved in chain elongation. The results low expression Ext1, and, as consequence, length is substantially reduced. In present study, mutant wild-type mouse were analyzed for...
The pathophysiology of congenital diaphragmatic hernia (CDH) is constituted by pulmonary hypoplasia and hypertension (PH). We previously reported successful treatment with imatinib a patient CDH. This study examines the effect antenatal administration on vasculature in rat model Pregnant rats were given nitrofen to induce Controls olive oil. Half CDH fetuses half controls treated antenatally E17-E21, rendering four groups: Control, Control+Imatinib, CDH, CDH+Imatinib. Lung sections obtained...
Background Stromal fibroblasts are important determinants of tumor cell behavior. They act to condition the microenvironment, influence growth, support angiogenesis and affect metastasis. Heparan sulfate proteoglycans, present both on stromal cells, interact with a large number ligands including growth factors, their receptors, structural components extracellular matrix. Being ubiquitously expressed in microenvironment heparan proteoglycans candidates for playing central roles tumor-stroma...
Synthetic tracheal grafts seeded with autologous bone marrow-mononuclear cells (BM-MNCs) have been described as becoming living and functional representing a promising option for replacement pathologies unamenable by segmental resection or repair. This study aimed to present the first long-term follow-up of these procedures in humans.We retrospectively analyzed 3 patients who received synthetic BM-MNCs implanted.Patient 1 was 37-year-old man mucoepidermoid carcinoma, first-ever human receive...
Generation of new cardiomyocytes is critical for cardiac repair following myocardial injury, but which kind stimuli most important cardiomyocyte regeneration still unclear. Here we explore if apoptotic stimuli, manifested through caspase activation, influences progenitor up-regulation and differentiation. Using mouse embryonic stem cells as a cellular model, show that sublethal activation caspases increases the yield while concurrently promoting proliferation differentiation...
The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterized. Here we demonstrate that can expand with characteristics cardiovascular progenitor from the MSC population hearts. Cells cultured on muscle laminin (LN)-based substrata in combination stimulation canonical Wnt/β-catenin pathway showed increased gene expression ISL1, OCT4, KDR, and NKX2.5. majority stained positive for PDGFR-α, NKX2.5, subpopulations also expressed...
Abstract Multipotent mesenchymal stromal cell (MSC) therapy and costimulation blockade are two immunomodulatory strategies being developed concomitantly for the treatment of immunological diseases. Both these have capacity to inhibit immune responses induce regulatory T cells; however, their ability synergize remains largely unexplored. In order study this, MSCs from C57BL/6 (H2b) mice were infused together with fully major histocompatibility complex-mismatched Balb/c (H2d) allogeneic islets...
Type 2 diabetes and cardiovascular disease are complex disorders involving metabolic inflammatory mechanisms. Here we investigated whether sCD93, a group XIV c-type lectin of the endosialin family, plays role in dysregulation or carotid intima-media thickness (IMT). Although no association was observed between sCD93 IMT, levels were significantly lower subjects with type (n = 901, mean ± SD 156.6 40.0 ng/mL) compared without 2,470, 164.1 44.8 ng/mL, P < 0.0001). Genetic variants...
It has been previously demonstrated that addition of anti-LFA-1 to a combination CTLA4Ig and anti-CD40L induces the permanent acceptance dopaminergic fetal pig xenografts when transplanted into brain wild-type mice. The purpose this study was test whether costimulation blockade also can induce adult islets C57BL/6 mice with streptozotocin-induced diabetes.Recipients were treated CTLA4Ig/anti-CD40L+/-anti-LFA-1 or isotype control antibodies during first week after transplantation. Half...
Background Microenvironmental interactions of the malignant clone with T cells are critical throughout natural history chronic lymphocytic leukemia (CLL). Indeed, clonal expansions and shared clonotypes exist between different CLL patients, strongly implying selection by antigens. Moreover, immunogenic neoepitopes have been isolated from clonotypic B cell receptor immunoglobulin sequences, offering a rationale for immunotherapeutic approaches. Here, we interrogated (TR) gene repertoire...
Aortic valve degeneration (AVD) is a life-threatening condition that has no medical treatment and lacks individual therapies. Although extensively studied with standard approaches, aetiologies behind AVD are unclear. We compared abundances of extracellular matrix (ECM) proteins from excised tissues 88 patients isolated normal tricuspid (TAV) congenital bicuspid aortic valves (BAV), quantified more than 1400 per ECM sample by mass spectrometry, demonstrated local preserves molecular cues the...
Mesenchymal stromal cells (MSCs), due to their regenerative and immunomodulatory properties, are therapeutically used for diseases, including heart failure. As early gestational-phase embryonic tissues exhibit extraordinary potential, fetal MSCs exposed inflammation offer a unique opportunity evaluate molecular mechanisms underlying preferential healing, investigate inherent abilities communicate with the immune system during development. The principal aim of this study was effects...
Mesenchymal stromal cells (MSCs) have shown great potential as a treatment for systemic inflammatory diseases, but their local regenerative properties are highly tissue- and site specific. Previous studies demonstrated that adult human MSCs respond to cytokines through the release of paracrine factors stimulate angiogenesis, they do not themselves differentiate into vascular structures in vivo. In this study, we used fetal cardiac (hfcMSCs) harvested during first trimester heart development...