High engraftment capacity of frozen ready-to-use human fecal transplants assessed in germ-free mice
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PROVIDER: PRJEB39960 | ENA |
REPOSITORIES: ENA
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Project description:Standardized preparation of frozen, live and ready-to-use transplants for microbiotherapy - short-term storage
| PRJEB30319 | ENA
Project description:Standardized preparation of frozen, live and ready-to-use transplants for microbiotherapy - conservative diluents and thawing conditions
| PRJEB30320 | ENA
Project description:Treatment of graft failure after allogeneic stem cell transplantation with mesenchymal stromal cells (MSC) is being evaluated clinically. MSC can exert their functions by the release of extracellular vesicles (EV). Our aim is to analyze changes induced in hematopoietic stem cells (HSC) after the incorporation of MSC-EV. MSC were isolated from healthy donors. MSC-EV were isolated by ultracentrifugation and characterized by flow cytometry (FC), Western-blot, electron microscopy and Nanosight. EV incorporation into HSC was analyzed by FC and confocal microscopy. To study HSC gene expression, RT-PCR and arrays were performed. Apoptosis and cell cycle were evaluated by FC and clonal growth by clonogenic assays in methylcellulose. The engraftment capacity of HSC was analyzed four weeks after transplantation in NOD-SCID mice. Our results showed that MSC-EV presented the characteristic morphology, size and inmunophenotype and were able to be incorporated into HSC. MSC-EV incorporation induced an a down-regulation of pro-apoptotic genes, an overexpression of genes involved in colony formation and cell proliferation together with an activation of the JAK-STAT pathway in HSC. A significant decrease in apoptosis (p=0.001), an increase of the percentage of cells in phase S and an increased CD44 expression (p=0.013) were confirmed by FC in HSC with MSC-EV. In addition, these HSC displayed a higher CFU-GM clonogenic potential (p=0.010). Finally, in the xenotransplantation model, the engraftment ability of human HSC with MSC-EV was significantly higher (p= 0.027). In summary, the incorporation of MSC-EV induces genomic and functional changes in HSC, increasing their clonogenic capacity and their engraftment ability.
2020-10-31 | GSE120803 | GEO
Project description:Microarray analysis of human kidneys with acute kidney injury (AKI) has been limited because such kidneys are seldom biopsied. However, all kidney transplants experience AKI, and early kidney transplants without rejection are an excellent model for human AKI: they are screened to exclude chronic kidney disease, frequently biopsied, and have extensive follow-up. We used histopathology and microarrays to compare indication biopsies from 28 transplants with AKI to 11 pristine protocol biopsies of stable transplants. Kidneys with AKI showed increased expression of 394 injury-repair response associated transcripts, including many known epithelial injury molecules (e.g. ITGB6, LCN2), tissue remodeling molecules (e.g. VCAN), and inflammation molecules (S100A8, ITGB3). Many other genes also predict the phenotype, depending on statistical filtering rules, including AKI biomarkers as HAVCR1 and IL18. Most mouse orthologs of the top injury-repair transcripts were increased in published mouse AKI models. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score AKI kidneys correlated with reduced function, future recovery, brain death, and need for dialysis, but not future graft loss. In contrast, histologic features of "acute tubular injury" did not correlate with function or with the molecular changes. Thus the injury-repair associated transcripts represent a massive coordinate injury-repair response of kidney parenchyma to AKI, similar to mouse AKI models, and provide an objective measure for assessing the severity of AKI in kidney biopsies and validation for the use of many AKI biomarkers.
2012-02-21 | GSE30718 | GEO
Project description:The transcriptomic effects of EGFR-inhibition by osimertinib on murine EGFR-mutant lung cancer transplants in a syngenic model were assessed.
2021-07-19 | E-MTAB-9883 | biostudies-arrayexpress
Project description:Neuropathic pain causes severe suffering and most patients are resilient to current therapies. A core element of neuropathic pain is the loss of inhibitory tone in the spinal cord. Previous studies have shown that foetal GABAergic neuron precursors can provide relief from pain. However, the source of these precursor cells and their multipotent status make them unsuitable for therapeutic use. Here we extend these findings by showing, for the first time, that spinally transplanted, terminally differentiated hiPSC-derived GABAergic (iGABAergic) neurons provide significant, long-term and safe relief from neuropathic pain induced by peripheral nerve injury in mice. Furthermore, iGABAergic Neuron transplants survive long term in the injured spinal cord and show evidence of synaptic integration. Together, this provides the proof in principle for the first viable GABAergic transplants to treat human neuropathic pain patients.
2020-01-23 | GSE115565 | GEO
Project description:Microarray analysis of human kidneys with acute kidney injury (AKI) has been limited because such kidneys are seldom biopsied. However, all kidney transplants experience AKI, and early kidney transplants without rejection are an excellent model for human AKI: they are screened to exclude chronic kidney disease, frequently biopsied, and have extensive follow-up. We used histopathology and microarrays to compare indication biopsies from 28 transplants with AKI to 11 pristine protocol biopsies of stable transplants. Kidneys with AKI showed increased expression of 394 injury-repair response associated transcripts, including many known epithelial injury molecules (e.g. ITGB6, LCN2), tissue remodeling molecules (e.g. VCAN), and inflammation molecules (S100A8, ITGB3). Many other genes also predict the phenotype, depending on statistical filtering rules, including AKI biomarkers as HAVCR1 and IL18. Most mouse orthologs of the top injury-repair transcripts were increased in published mouse AKI models. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score AKI kidneys correlated with reduced function, future recovery, brain death, and need for dialysis, but not future graft loss. In contrast, histologic features of "acute tubular injury" did not correlate with function or with the molecular changes. Thus the injury-repair associated transcripts represent a massive coordinate injury-repair response of kidney parenchyma to AKI, similar to mouse AKI models, and provide an objective measure for assessing the severity of AKI in kidney biopsies and validation for the use of many AKI biomarkers. AKI biopsies sample names and CEL files are from GSE21374. All consenting renal transplant patients undergoing biopsies for cause as standard of care between 09/2004 and 10/2007 at the university of Alberta or between 11/2006 and 02/2007 at the University of Illinois were included in the analysis. In addition to the cores required for standard histopathology, we collected one core for gene expression studies. the relationship between gene expression in the biopsy and subsequent graft loss was analyzed. This dataset is part of the TransQST collection.
2012-02-21 | E-GEOD-30718 | biostudies-arrayexpress
Project description:Heterotopic cardiac transplants were constructed in male Wistar Furth (allograft donor) and ACI (host) rats. Rats were divided into three groups consisting of no treatment, treatment with a sub-therapeutic dose of cyclosporin A, and treated with combination of a sub-therapeutic dose of cyclosporin A and allochimeric peptide. The allografts were harvested at defined periods post-transplantation and RNA was harvested to monitor gene expression changes resulting from the various treatments in T-cells and in heart cells.
2009-11-11 | GSE15074 | GEO
Project description:Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions including leukemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here, we developed a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We used this system to conduct a chemical screen and identified epoxyeicosatrienoic acids (EET) as a family of lipids that enhance HSPC engraftment. EETs’ pro-haematopoietic effects are conserved in the developing zebrafish, where this molecule promotes HSPC specification through activating a unique AP-1/runx1 transcription program autonomous to the haemogenic endothelium. This effect requires the activation of PI3K pathway, specifically PI3Kg. In adult HSPCs, EETs induce transcriptional programs including AP-1 activation, modulating multiple cellular processes, such as migration, to promote engraftment. Finally, we demonstrated that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study established a novel method to explore the molecular mechanisms of HSPC engraftment, and discovered a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.
2015-07-13 | GSE66767 | GEO
Project description:Human pluripotent stem cell-derived cardiomyocytes (CMs) are a promising tool for cardiac cell therapy. To optimize graft cells for cardiac reconstruction, we compared the engraftment efficiency of intramyocardially-injected undifferentiated-induced pluripotent stem cells (iPSCs), day4 mesodermal cells, and day8, day20, and day30 purified iPSC-CMs after initial differentiation by tracing the engraftment ratio (ER) using in vivo bioluminescence imaging. This analysis revealed the ER of day20 CMs was significantly higher compared to other cells. Transplantation of day20 CMs into the infarcted hearts of immunodeficient mice showed significant functional improvement. Moreover, the imaging signal and ratio of Ki67-positive CMs at 3 months post injection indicated engrafted CMs proliferated in the host heart. Although this graft growth reached a plateau at 3 months, histological analysis confirmed progressive maturation from 3 to 6 months. These results suggested that day20 CMs had very high engraftment, proliferation, and therapeutic potential in host mouse hearts. Differentiated cells, N=10 Undifferentiated pluripotent stem cells, N=1 Heart samples, N=6
2016-07-03 | E-GEOD-60634 | biostudies-arrayexpress