Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA203304 | ENA |
REPOSITORIES: ENA
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Project description:We analyzed the changes in the spinal cord transcriptome after a spinal cord contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. 52 total samples were analyzed in 13 different groups. Each group include 4 samples and each one were analyzed as a biological replica. The intact animals were used as control of injury. The vehicle (VHC) groups were used as control of transplantation procedure. The MSC or OEC graft were injected at the day of injury (acute graft) or seven days after injury (delayed graft). The samples from engrafted animals were obtained at 2 or 7 days after cell transplantation. To determine the effects of MSC or OEC transplantation, the expression value of each engrafted sample were compared with correspondent VHC group.
2013-10-16 | E-GEOD-46988 | biostudies-arrayexpress
Project description:We analyzed the changes in the spinal cord transcriptome after a spinal cord contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting.
2013-10-16 | GSE46988 | GEO
Project description:Olfactory ensheathing cells (OECs) are the only glial cells that support the olfactory sensory neurons which undergo adult neurogenesis and continually project their axons to glomeruli in the olfactory bulbs. We used single cell RNA sequencing to study the gene expression programs of OECs and to determine the diversity of purified OECs previously shown to promote spinal cord injury repair. Our analyses revealed five subtypes of OECs, each expressing unique marker genes and pathways indicative of progenitor, axonal regeneration, migration, or microglia-like functions. As expected, we found substantial overlap of OEC genes with those of Schwann cells, but also with astrocytes, oligodendrocytes and microglia. We experimentally confirmed the classic marker genes of the OEC subtypes and provide evidence that Reelin and Connective Tissue Growth Factors are secreted by multiple OEC subtypes. Our results support that adult OECs are a hybrid glia including some with progenitor characteristics and that they likely carry out diverse functions related to injury repair and axonal regeneration.
2022-10-13 | GSE215247 | GEO
Project description:<p><strong>BACKGROUND:</strong> Ischemia/reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal Stromal Cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy, however, their full potential in treating AKI remains unknown.</p><p><strong>METHODS:</strong> In this study, we employed an in vitro model of chemically-induced ischemia using antimycin A combined with 2-deoxy-D-glucose to induce ischemic injury in proximal tubule epithelial cells. Afterwards, we evaluated the effects of MSC secretome, CM or EVs obtained from adipose tissue, bone marrow and umbilical cord, on ameliorating the detrimental effects of ischemia. To assess the damage and treatment outcomes, we analyzed cell morphology, mitochondrial health parameters (mitochondrial activity, ATP production, mass and membrane potential) and overall cell metabolism by metabolomics.</p><p><strong>RESULTS:</strong> Our findings show that ischemic injury caused cytoskeletal changes confirmed by disruption of the F-actin network, energetic imbalance as revealed by a 50% decrease in the oxygen consumption rate, increased oxidative stress, mitochondrial dysfunction and reduced cell metabolism. Upon treatment with MSC secretome, the morphological derangements were partly restored and ATP production increased by 40-50%, with umbilical cord-derived EVs being most effective. Furthermore, MSC treatment led to phenotype restoration as indicated by an increase in cell bioenergetics, including increased levels of glycolysis intermediates, as well as an accumulation of antioxidant metabolites.</p><p><strong>CONCLUSION:</strong> Our in vitro model effectively replicated the in vivo-like morphological and molecular changes observed during ischemic injury. Additionally, treatment with MSC secretome ameliorated proximal tubule damage, highlighting its potential as a viable therapeutic option for targeting AKI.</p>
2023-10-16 | MTBLS6279 | MetaboLights
Project description:Adult neural stem cells (aNSCs) show multilineage differentiation potential influenced by intrinsic and extrinsic signaling cues. We and others have shown that stimulation of aNSCs with bone marrow mesenchymal stem cell (MSC) secreted factors substantially enhances in vitro oligodendrogenesis at an expense of astrogenesis by yet unknown mechanisms (Rivera et al. 2006, Jadasz et al. 2013; 2018, Rivera et al., 2019). In the present study, we demonstrate that aNSCs pre-treated with MSC secretomes for different periods in vitro preferentially differentiate to oligodendrocytic cells in vivo after transplantation into the adult rat spinal cord. Analysis of different time points after transplantation revealed a stable survival rate of transplanted aNSCs and an emphasized pro-oligodendroglial differentiation in response to MSC secreted factors. MSC derived secretomes were then analyzed by mass spectrometry-based proteomics and label-free quantification to identify secreted proteins contributing to oligodendroglial lineage fate determination. To exclude possible contaminants derived from dead cells or serum, our approach includes a comparison of the abundances of proteins present in MSC derived secretomes with corresponding proteins in cell lysates (Grube et al., 2018, Schira-Heinen et al., 2019).
2020-06-18 | PXD018231 | Pride
Project description:Effectively reducing the inflammatory response after spinal cord injury (SCI) is a challenging clinical problem and the subject of active investigation. This study employed a porous scaffold-based three dimensional long-term culture technique to obtain human umbilical cord mesenchymal stem cell (hUC-MSC)-derived Small Extracellular Vesicles (sEVs) (three dimensional culture over time, the “4D-sEVs”). Moreover, the vesicle size, number, and inner protein concentrations of the MSC 4D-sEVs contained altered protein profiles compared with those derived from 2D culture conditions. A proteomics analysis suggested broad changes, especially significant upregulation of Epidermal Growth Factors Receptor (EGFR) and Insulin-like Growth Factor Binding Protein 2 (IGFBP2) in 4D-sEVs compared with 2D-sEVs. The endocytosis of 4D-sEVs allowed for the binding of EGFR and IGFBP2, leading to downstream STAT3 phosphorylation and IL-10 secretion and effective induction of macrophages/microglia polarization from the pro-inflammatory M1 to anti-inflammatory M2 phenotype, both in vitro and in the injured areas of rats with compressive/contusive SCI. The reduction in neuroinflammation after 4D-sEVs delivery to the injury site epicenter led to significant neuroprotection, as evidenced by the number of surviving spinal neurons. Therefore, applying this novel 4D culture-derived Small Extracellular Vesicles could effectively curb the inflammatory response and increase tissue repair after SCI.
2023-07-20 | PXD040516 | Pride
Project description:We generated iPSCs from human intervertebral disc cells which were obtained during spine fusion surgery of patients with spinal cord injury. The disc cell-derived iPSCs (diPSCs) showed similar characteristics to human embryonic stem cells (hESCs) and were efficiently differentiated into neural progenitor cells (NPCs) with the capability of differentiation into mature neurons in vitro. To examine whether the transplantation of NPCs derived from the diPSCs showed therapeutic effects, the NPCs were transplanted into mice at 9 days post-spinal cord injury. We detected a significant amelioration of hind limb dysfunction during the follow up recovery periods. Histological analysis at 5 weeks post-transplantation, we could identify undifferentiated human NPCs (Nestin+) as well as early (TUJ1+) and mature neurons (MAP2+) derived from the NPCs. Furthermore, the NPC transplantation demonstrated a preventive effect on the spinal cord degeneration resulting from the secondary injury. This study revealed that the intervertebral disc, a M-bM-^@M-^\to-be-wasteM-bM-^@M-^] tissue, removed from the surgical procedure, could provide a unique opportunity to study iPSCs derived from hardly accessible somatic cells in normal situation and also be a useful therapeutic resource to generate autologous neural cells to treat patients suffering from spinal cord injury. Total RNA was isolated using the NucleoSpin RNA II Kit (Macherey-Nagel, Duren, Germany, www.mn-net.com) according to the manufacturerM-bM-^@M-^Ys suggestions and was utilized for a genome-wide gene expression profiling experiment using the Illumina array (Illumina, San Diego, CA, USA, www.illumina.com) at Macrogen (Macrogen, Seoul, Korea, www.macrogen.com).
2015-01-15 | E-GEOD-64964 | biostudies-arrayexpress
Project description:Increasing studies suggested the treatment potential of mesenchymal stem cells in variety diseases. Evidence showed that MSCs could promote injured tissue repair and improve disease mortality. These indicated that MSC transplantation may be an ideal candidate for cholestasis treatment.We found that MenSC transplantation could significantly improve the symptoms and pathological changes of DDC-induced cholestasis liver injury in mice.
2022-02-16 | PXD028425 | Pride
Project description:We generated iPSCs from human intervertebral disc cells which were obtained during spine fusion surgery of patients with spinal cord injury. The disc cell-derived iPSCs (diPSCs) showed similar characteristics to human embryonic stem cells (hESCs) and were efficiently differentiated into neural progenitor cells (NPCs) with the capability of differentiation into mature neurons in vitro. To examine whether the transplantation of NPCs derived from the diPSCs showed therapeutic effects, the NPCs were transplanted into mice at 9 days post-spinal cord injury. We detected a significant amelioration of hind limb dysfunction during the follow up recovery periods. Histological analysis at 5 weeks post-transplantation, we could identify undifferentiated human NPCs (Nestin+) as well as early (TUJ1+) and mature neurons (MAP2+) derived from the NPCs. Furthermore, the NPC transplantation demonstrated a preventive effect on the spinal cord degeneration resulting from the secondary injury. This study revealed that the intervertebral disc, a “to-be-waste” tissue, removed from the surgical procedure, could provide a unique opportunity to study iPSCs derived from hardly accessible somatic cells in normal situation and also be a useful therapeutic resource to generate autologous neural cells to treat patients suffering from spinal cord injury.
2015-01-15 | GSE64964 | GEO
Project description:Olfactory ensheathing cells (OECs) are neural crest-derived glia that ensheath bundles of olfactory axons from their peripheral origins in the olfactory epithelium to their central targets in the olfactory bulb. We took an unbiased laser microdissection and differential RNA-seq approach, validated by in situ hybridisation, to identify candidate molecular mechanisms underlying mouse OEC development and differences with the neural crest-derived Schwann cells developing on other peripheral nerves. We identified 25 novel markers for developing OECs in the olfactory mucosa and/or the olfactory nerve layer surrounding the olfactory bulb, of which 15 were OEC-specific, i.e., not expressed by Schwann cells. One pan-OEC-specific gene, Ptprz1, encodes a receptor-like tyrosine phosphatase that blocks oligodendrocyte differentiation. Mutant analysis suggests Ptprz1 may also act as a brake on OEC differentiation, and that its loss disrupts olfactory axon targeting. Overall, our results provide new insights into OEC development and the diversification of neural crest-derived glia.
2020-06-02 | GSE138596 | GEO