Project description:<p><strong>BACKGROUND:</strong> Perioperative neurocognitive disorder (PND) is a key complication affecting older individuals after anesthesia and surgery. Failure to translate multiple pharmacological therapies for PND from preclinical studies to clinical settings has necessitated the exploration of novel therapeutic strategies. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) treatment has emerged as a promising therapeutic strategy for treating neurodegenerative diseases and has the potential to translate basic science into clinical practice. In this study, we investigated the effects and underlying mechanism of hUC-MSCs on PND in aged mice.</p><p><strong>METHODS:</strong> hUC-MSCs were isolated from an infant umbilical cord and identified using flow cytometry and differentiation assays. We established PND model by undergoing aseptic laparotomy under isoflurane anesthesia maintaining spontaneous ventilation in 18-month-old male C57BL/6 mice. hUC-MSCs were slowly injected into mice by coccygeal vein before anesthesia. Cognitive function, neuroinflammation, neuroplasticity, endogenous neurogenesis and brain-derived neurotrophic factor (BDNF) were assessed. To determine the mechanisms underlying by which hUC-MSCs mediate their neuroprotective effects in PND, K252a, an antagonist of BDNF receptor, was administered intraperitoneally before surgery. Hippocampal BDNF/TrkB/CREB signaling pathway and metabolomic signatures were evaluated.</p><p><strong>RESULTS:</strong> hUC-MSC treatment ameliorated the learning and memory impairment in aged mice with PND. The downstream effects were the suppression of neuroinflammatory responses and restoration of neurogenesis and neuroplasticity dysregulation. Interestingly, the level of mature BDNF, but not that of proBDNF, was increased in the hippocampus after hUC-MSC treatment. Further analysis revealed that the improved cognitive recovery and the restoration of neurogenesis and neuroplasticity dysregulation elicited by exposure to hUC-MSCs were, at least partially, mediated by the activation of the BDNF/TrkB/CREB signaling pathway. Untargeted metabolomic further identified lipid metabolism dysfunction as potential downstream of the BDNF/TrkB/CREB signaling pathway in hUC-MSC-mediated neuroprotection for PND.</p><p><strong>CONCLUSIONS:</strong> Our study highlights the beneficial effects of hUC-MSC treatment on PND and provides a justification to consider the potential use of hUC-MSCs in the perioperative period.</p>
Project description:Exosomes derived from mesenchymal stem cells (MSCs) have shown to have effective application prospects in the medical field, but exosome yield is very low. The production of exosome mimetic vesicles (EMVs) by continuous cell extrusion leads to more EMVs than exosomes, but whether the protein compositions of MSC-derived EMVs (MSC-EMVs) and exosomes (MSC-exosomes) are substantially different remains unknown. The purpose of this study was to conduct a comprehensive proteomic analysis of MSC-EMVs and MSC-exosomes and to simply explore the effects of exosomes and EMVs on wound healing ability. This study provides a theoretical basis for the application of EMVs and exosomes.In this study, EMVs from human umbilical cord MSCs (hUC MSCs) were isolated by continuous extrusion, and exosomes were identified after hUC MSC ultracentrifugation. A proteomic analysis was performed, and 2,315 proteins were identified. The effects of EMVs and exosomes on the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by cell counting kit-8, scratch wound, Transwell and tubule formation assays. A mouse mode was used to evaluate the effects of EMVs and exosomes on wound healing . Bioinformatics analyses revealed that 1,669 proteins in both hUC MSC-EMVs and hUC MSC-exosomes play roles in retrograde vesicle-mediated transport and vesicle budding from the membrane. The 382 proteins unique to exosomes participate in extracellular matrix organization and extracellular structural organization, and the 264 proteins unique to EMVs target the cell membrane. EMVs and exosomes can promote wound healing and angiogenesis in mice and promote the proliferation, migration and angiogenesis of HUVECs.
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: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:Human umbilical cord mesenchymal stem cells maintained multipotency and immunosuppressive ability when being cultured in chemical defined serum free medium, but gained different gene expression profile. We used microarrays to identify the transcriptional difference between human umbilical cord mesenchymal stem cells cultured in serum containing medium and chemical defined serum free medium. human umbilical cord mesenchymal stem cells were cultured in conventional serum containing medium and chemical defined serum free medium separately. Total RNA was extracted and hybridized on Affymetrix microarrays.
Project description:Mesenchymal stem cells (MSCs) have been shown to exert therapeutic effects on various autoimmune diseases. However, such therapeutic effect is not always achieved. Among many reasons, MSC culture methodologies may account for the these differences. It is known that oxygen concentration could profoundly affect the properties of MSCs. Therefore, we compared human umbilical cord derived MSCs cultured under hypoxic and normoxic conditions. We used microarrays to profile the gene expression of human umbilical cord derived MSCs under 10% oxygen and normoxia conditions.
Project description:Human umbilical cord mesenchymal stem cells maintained multipotency and immunosuppressive ability when being cultured in chemical defined serum free medium, but gained different gene expression profile. We used microarrays to identify the transcriptional difference between human umbilical cord mesenchymal stem cells cultured in serum containing medium and chemical defined serum free medium.
Project description:Application of umbilical cord mesenchymal stem cell-derived conditioned media (HUCMSC-CM) to treat severe, progressive PAH. Serial infusions of HUCMSC-CM resulted in marked clinical and hemodynamic improvement after 6 months, and showed no adverse events. Differential expression analysis between conditioned media and cells was used to identify molecular processes with a putative role in treatment benefit.