A5091419246- Mesenchymal stem cell research
- Tissue Engineering and Regenerative Medicine
- Neonatal Respiratory Health Research
- Liver physiology and pathology
- Pancreatic function and diabetes
- Immune cells in cancer
- Electrospun Nanofibers in Biomedical Applications
- Liver Disease Diagnosis and Treatment
- Respiratory Support and Mechanisms
- Liver Diseases and Immunity
- Heat shock proteins research
- Cancer Cells and Metastasis
- Biomedical Ethics and Regulation
- CRISPR and Genetic Engineering
- Wound Healing and Treatments
- Pluripotent Stem Cells Research
- Muscle Physiology and Disorders
- Extracellular vesicles in disease
- Mechanical Circulatory Support Devices
- Circular RNAs in diseases
- Salivary Gland Disorders and Functions
- Lung Cancer Diagnosis and Treatment
- Vascular Malformations and Hemangiomas
- Chronic Kidney Disease and Diabetes
- Congenital heart defects research
Orbsen Therapeutics (Ireland)
2015-2024
Ollscoil na Gaillimhe – University of Galway
2015-2021
Novartis (Switzerland)
2005-2007
University College London
2004
<h3>Background</h3> Mesenchymal stromal cells (MSCs) demonstrate considerable promise in preclinical acute respiratory distress syndrome models. We wished to determine the efficacy and mechanisms of action human MSCs (hMSCs) setting lung injury induced by prolonged <i>Escherichia coli</i> pneumonia rat. <h3>Methods</h3> Adult male Sprague Dawley rats underwent intratracheal instillation <i>E. bacteria all experiments. In <i>Series 1,</i> animals were randomised intravenous administration of:...
Significance Statement Mesenchymal stromal cells (MSCs) may offer a novel therapy for diabetic kidney disease (DKD), although clinical translation of this approach has been limited. The authors present findings from the first, lowest dose cohort 16 adults with type 2 diabetes and progressive DKD participating in randomized, placebo-controlled, dose-escalation phase 1b/2a trial next-generation bone marrow–derived, anti-CD362 antibody–selected allogeneic MSCs (ORBCEL-M). A single intravenous...
Mesenchymal stem cells (MSC) represent a promising therapeutic approach in many diseases view of their potent immunomodulatory properties, which are only partially understood. Here, we show that the endothelium is specific and key target MSC during immunity inflammation. In mice, inhibit activation proliferation endothelial remote inflamed lymph nodes (LNs), affect elongation arborization high venules (HEVs) T-cell homing. The proteomic analysis secretome identified tissue inhibitor...
MicroRNAs (miRNAs) are deregulated in cancer and have been shown to exhibit both oncogenic tumor suppressive functions. Although the functional effects of several miRNAs elucidated, those many remain be discovered. In silico analysis identified microRNA-206 (miR-206) binding sites 3'-untranslated regions (3'-UTR) mouse human CCND1 gene. Cyclin D1 is a recognized oncogene involved direct phosphorylation retinoblastoma (Rb) protein promoting cell cycle transition from G1 S. miR-206...
The tyrosine kinase inhibitor imatinib mesylate (Gleevec) has been demonstrated to protect various cell types from death by inhibition of Abelson (c-Abl). aim the present study was establish whether protects insulin producing beta-cell different apoptosis promoting agents in vitro and counteracts streptozotocin-induced diabetes NMRI mice. We observe that attenuated actions several substances. In addition, mice injected with streptozotocin did not develop when given imatinib. beneficial...
The analysis of mesenchymal stromal cells secretome is fundamental to identify key players processes involving these cells. Truly secreted proteins may be difficult detect in MS based conditioned media (CM) due supplemented with fetal bovine serum (FBS). We compared different growth conditions determine the effect varying FBS concentration on number and quantity truly human vs contaminating proteins. results suggest that minimize interference should grown presence until confluence...
Abstract Articular cartilage lacks an intrinsic repair capacity and due to the ability of mesenchymal stem cells (MSCs) differentiate into chondrocytes, MSCs have been touted as a cellular source regenerate damaged cartilage. However, number prevailing concerns for such treatment remain. Generally, administration defect results in poor regeneration with repaired consisting primarily fibro-cartilage rather than hyaline Methods that improve chondrogenic potential transplanted vivo may be...
Cell sheet tissue engineering requires prolonged in vitro culture for the development of implantable devices. Unfortunately, lengthy is associated with cell phenotype loss and substantially higher cost goods, which collectively hinder clinical translation commercialisation engineered medicines. Although macromolecular crowding has been shown to enhance accelerate extracellular matrix deposition, whilst maintaining cellular phenotype, optimal agent still remains elusive. Herein, we evaluated...
Abstract Tumour stromal cells support tumourigenesis. We report that Syndecan‐2 ( SDC2 ) is expressed on a nonepithelial, nonhaematopoietic, nonendothelial cell population within breast cancer tissue. In vitro , syndecan‐2 modulated TGFβ signalling SMAD7, PAI‐1 ), migration and immunosuppression of patient‐derived tumour‐associated (TASCs). an orthotopic immunocompromised model, overexpression in TASCs significantly enhanced tumour growth metastasis, whereas reducing levels attenuated PAI‐1,...
Mesenchymal stem/stromal cells (MSC) are an immunomodulatory cell population which under preclinical and clinical investigation for a number of inflammatory conditions including transplantation. In this study, well-established rat corneal transplantation model was used to test the ability human MSC prolong allograft rejection-free survival using pre-transplant intravenous infusion protocol previously shown be efficacious with allogeneic MSC. Surprisingly, administration had no effect on...
Abstract Background Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have been proposed as an alternative to therapy, creating new possible delivery modalities such nebulisation. We wished investigate the therapeutic potential of directly nebulised MSC-EVs in mitigation Escherichia coli -induced pneumonia. Methods EV size, surface markers and miRNA content were assessed pre- post-nebulisation. BEAS2B A459 lung cells exposed lipopolysaccharide (LPS) treated with bone marrow...
Mesenchymal stromal cells (MSCs) ameliorate pre-clinical sepsis and sepsis-associated acute kidney injury (SA-AKI) but clinical trials of single-dose MSCs have not indicated robust efficacy. This study investigated immunomodulatory effects a novel MSC product (CD362-selected human umbilical cord-derived [hUC-MSCs]) in mouse endotoxemia polymicrobial models. Initially, mice received intra-peritoneal (i.p.) lipopolysaccharide (LPS) followed by single i.p. doses hUC-MSCs or vehicle. Next,...
Mesenchymal stromal cells (MSCs) have a multimodal, immunomodulatory mechanism of action and are now in clinical trials for single organ systemic sepsis. However, number practicalities around source, homogeneity therapeutic window remain to be determined. Here, we utilised conditioned medium from CD362+-sorted umbilical cord-human MSCs (UC-hMSCs) series vitro anti-inflammatory assays the cryopreserved themselves severe (Series 1) or moderate 2+3) caecal ligation puncture (CLP) rodent model....
Processed pseudogenes emerge by reverse transcription of spliced mRNAs followed incorporation the resultant cDNA into genome. Their genesis requires that retrotransposition occurs within germ line, a provision significantly limits random distribution source genes. We previously identified embryonic stem cell-specific genes as an enriched retropseudogene origin. Nanog, Oct4, and Dppa3 (Stella/PGC7) presented for >30 processed human In current study, we extended our previous analysis focused...
Using a gene clustering strategy we determined intracellular pathway relationships within skeletal myotubes in response to an acute heat stress stimuli. Following shock, the transcriptome was analyzed by microarray temporal fashion characterize dynamic relationship of signaling pathways. Bioinformatics analyses exposed coordination functionally-related sets, depicting mechanism-based responses shock. Protein turnover-related pathways were significantly affected including protein folding,...
Abstract Peripheral arterial disease (PAD) is strongly associated with lower-extremity muscle wasting. Hallmark features of PAD skeletal pathology include a loss mass, reduced strength and physical performance, as well increased inflammation, fibrosis adipocyte infiltration, among others. At molecular level, ischaemia has also been gene microRNA (miRNA) dysregulation. Mesenchymal stromal cells (MSCs) have previously reported to enhance regeneration improve function in variety injuries. The...
Background: Mesenchymal stromal cells (MSCs) are an attractive cell type for therapy given their immunomodulatory, anti-fibrotic, and endothelial-protective features. The heparin sulfate proteoglycan, syndecan-2/CD362, has been identified as a functional marker MSC isolation, allowing one to obtain homogeneous product that meets regulatory requirements clinical use. We previously assessed the impact of wild-type (WT), CD362 − , + MSCs on local changes in protein distribution left ventricular...
Background and objectives To simulate the cost-effectiveness of Mesenchymal Stromal Cell (MSC) therapy compared to sodium/glucose co-transporter 2 inhibitors (SGLT2i) or usual care (UC) in treating patients with Diabetic Kidney Disease (DKD). Design, setting, participants, measurements This Markov-chain Monte Carlo model adopted a societal perspective simulated 10,000 DKD eligible for MSC alongside UC using lifetime horizon. cohort was an SGLT2i arm only arm. Model input data were extracted...