Project description:screening of signature deterimes the individual variations in the therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells There is paucity of information whether human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) from separate donors might have different effects on improving myocardial repair after myocardial infarction (MI). We screened cell surface genes by the comparing the cells that showed the best and worst efficacy, respectively, in repairing the infarcted myocardium of rats.
Project description:screening of signature deterimes the individual variations in the therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells There is paucity of information whether human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) from separate donors might have different effects on improving myocardial repair after myocardial infarction (MI).
Project description:Unrestricted Somatic Stem Cells (USSC) are a cell population derived from umbilical cord blood. They have been shown to have greater plasticity than mesenchymal stem cells, and are being investigated as a therapeutic option for many disease states, including cardiovascular disease.<br><br>In this study, we aimed to evaluate the efficacy of USSC on treating acute myocardial infarction (MI). We compared the effectiveness of USSC to the more widely studied bone marrow derived mesenchymal stem cell. Finally, we investigated whether pre-conditioning USSC prior to administration enhances their effectiveness. We determined effectiveness primarily using cardiac ultrasound, and supported these findings with histological analyses.<br><br>We observed that pre-conditioned (guided) USSC had the most significant beneficial effect on cardiac function. (Pre-conditioned cells were grown in serum-free F12 media was supplemented with 50ng/ml Basic Fibroblast Growth Factor (bFGF), 20ng/ml Hepatocyte Growth Factor (HGF) and 20ng/ml Bone Morphogenetic Protein 2 (BMP2)). We performed microarray analysis of guided USSC and unmodified USSC to compare the gene expression profile of both cell populations, in order to evaluate whether any specific genes, or gene groups, were involved in mediating this beneficial effect.<br>
Project description:Human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display special interest as universal and feasible add-on therapy for myocardial infarction (MI). In this study, UCM-MSC from two umbilical cords, UC-A and UC-B, were transplanted in a murine MI model to investigate consistency and durability of the therapeutic benefits. Both cellular products supported sustained and long-term beneficial therapeutic effect. In vitro, the two cell products displayed similar ability to induce the formation of vessel-like structures and comparable transcriptome in normoxia and hypoxia, apart from expression differences in a small subset of genes associated with MHC Class I. These findings support that UCM-MSC are strong candidates to assist the treatment of MI whilst calling for the discussion on methodologies to characterize and select best performing UCM-MSC before clinical application.
Project description:Mesenchymal stromal cells are a potential therapeutic for Acute Respiratory Distress Syndrome due to COVID-19, with pleiotropic immunomodulatory and reparative properties.This study investigated the safety and efficacy of ORBCEL-C (CD362 enriched umbilical cord-derived Mesenchymal Stromal Cells) in this patient population.
Project description:Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). In this study, we investigated the outcome of the delivery of hUCM-MSC after reperfusion in a translational model of AMI in swine. We have found that intracoronary injection of the cell product was associated with improved systolic function and that improvement in mechanical performance. This did not depend on the reduction of morphological infarct size alone, despite treated animals showing signs of less adverse remodeling.
Project description:Mesenchymal stem cells (MSC) have emerged as potent therapeutic tool for a number of pathologies, including immune ones. However, unwelcome effects of MSC on the blood coagulation were revealed in some cases, which require more in-depth analysis. In this study, we explored the trombotic properties of human MSC from umbilical cord. We revealed strong procoagulant effects of umbilical cord MSC toward human and rat whole blood and platelets-free plasma using rotational thromboelastometry and thrombodynamics tests. The similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EV). In order to suggest approaches to avoid unwanted effects we studied the impact of heparin supplement on MSC/EV procoagulation properties. We found that therapeutic doses of unfractionated heparin injected in the patient's blood (administered in vivo) did not abrogate the procoagulant properties of MSC. Mass-spectrometry analysis of proteins of MSC and EV involved in coagulation-associated pathways was used to evaluate mechanisms of protrombotic effects.
Project description:Studying the safety and efficacy of two treatment protocols for Multiple sclerosis (MS) patients using Mesenchymal Stromal/Stem Cells MSCs subtype derived from the umbilical cord; UC-MSCs and their secretome
Project description:Quantitative shotgun proteomic analysis (TMT) of the effect of inhibition of MIR21 in the EV protein cargo of human, Umbilical cord-derived Mesenchymal Stem Cells.
Project description:Interventions: Test group:Postoperative adjuvant chemotherapy plus infusion of NK cells derived from human umbilical cord blood;control group:Postoperative adjuvant chemotherapy
Primary outcome(s): Recurrence and metastasis rates
Study Design: Parallel
