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:Transcriptional profiling of human peripheral mononuclear cells in patients with leukemic cutaneous T-cell lymphoma (CTCL): a pilot study of effects of extracorporeal photopheresis (ECP) in clinically responsive and non-responsive/resistant patients
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: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:Expression data from hiPS lines after commitment towards mesenchymal lineage (hiPS-MSC) and expression data of mesenchymal lines (MSC), used as positive control of commitment. Following this, hiPS-MSC and MSC are seeded on scaffold to differentiate in a ligamentous (middle) and osseous (edges) part (post 21 days 3D differentiation) We used microarrays to validate efficient commitment of hiPS to generate hiPS-MSC and do whole transcriptome comparison of hiPS-MSC vs isolated MSC (positive control) and then compare the enhanced biological functions after differentiation of these cells on a scaffold
Project description:Integrating stem cell therapies into clinical settings faces several challenges, particularly in achieving the high cell yields necessary for attaining therapeutic doses. Preconditioning with hypoxic conditions has shown promise in enhancing the mesenchymal stem cells (MSCs)’ reparative capabilities of the central nervous system. Recent evidence suggests that oxygen concentration and exposure duration can shape MSCs’ phenotypes, supporting the need for further optimization of this strategy in a way to achieve maximal repair. Methods: Wistar Han rat pups from both sexes underwent hypoxic-ischemic (HIE) brain injury at postnatal day 10 using the Rice-Vannucci model and were treated with umbilical cord derived-MSCs (UC-MSCs) preconditioned with prolonged mild hypoxia (MH; 5% oxygen for 48 hours) or short severe hypoxia (SSH; 0.1% oxygen for 24 hours) two days later. Results: Our results show that UC-MSCs’ were able to alleviate motor and cognitive deficits caused by the HI brain lesion. To investigate the molecular effects of hypoxia-preconditioned MSCs in the neonatal brain post-HIE, we employed untargeted proteomics on ipsilesional brain samples from control, HIE, HIE treated with naïve UC-MSCs, and HIE treated with SSH-preconditioned UC-MSCs groups, 30 days after lesion induction. This approach identified protein signatures related to injury and therapeutic intervention. Pathway enrichment analysis further revealed that administration of UC-MSCs preconditioned with short severe hypoxia significantly impacted neural signaling, protein synthesis, and energy metabolism pathways, pointing to long-term mechanisms that may support neuronal repair. Conclusion: These findings enhance our understanding of hypoxia-preconditioning in MSCs therapy in driving a positive therapeutic response, supporting the development of more effective and feasible treatments for neonatal hypoxic-ischemic brain injury.
Project description:Acute metabolic challenges provide insight on how the body responds to metabolic stress. In this study, we assessed transcriptomic response in peripheral blood mononuclear cells (PBMC) to an acute lipid challenge.
Project description:Acute metabolic challenges provide insight on how the body responds to metabolic stress. In this study, we assessed transcriptomic response in peripheral blood mononuclear cells (PBMC) to an acute glucose challenge.