Pharmacologically enhanced regulatory hematopoietic stem cells (HSC.Regs) reverts experimental autoimmune diabetes (Mouse)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE167323 | GEO | 2022/01/18
REPOSITORIES: GEO
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Project description:Ex-vivo pharmacological modulation enhances the immunoregulatory and trafficking properties of HSCs which mitigated autoimmune diabetes and other autoimmune disorders. We used GeneChip microarrays to compare the whole transcriptomes of vehicle (DMSO) and dmPGE2 (10uM) + Dexamenthasone (uM) modulated human CD34+ HSPCs.
2022-01-18 | GSE167269 | GEO
Project description:Pharmacologically enhanced regulatory hematopoietic stem cells (HSC.Regs) reverts experimental autoimmune diabetes
| PRJNA704027 | ENA
Project description:Pharmacologically enhanced regulatory hematopoietic stem cells (HSC.Regs) reverts experimental autoimmune diabetes (Mouse)
| PRJNA704315 | ENA
Project description:Transplantation with low numbers of hematopoietic stem cells (HSCs), found in many of the publically accessible cryopreserved umbilical cord blood (UCB) units, leads to delayed time to engraftment, high graft failure rates, and early mortality in many patients. A chemical screen in zebrafish identified the prostaglandin compound, 16,16 dimethyl prostaglandin E2 (dmPGE2), to be a critical regulator of hematopoietic stem cell homeostasis. We hypothesized that an ex vivo modulation with dmPGE2 prior to transplantation would lead to enhanced engraftment by increasing the “effective” dose of hematopoietic stem cells (HSCs) in cord blood. A phase I trial of reduced-intensity double UCB transplantation was performed to evaluate safety, rates of engraftment and fractional chimerism of dmPGE2 enhanced UCB units. To explore potential causes of the lack of enhanced efficacy in the first cohort, we characterized HSCs to determine whether the prostaglandin pathway was being activated under the ex vivo incubation conditions (4°C, 10µM dmPGE2, 60 minutes). Incubation conditions were identified (37°C, 10µM dmPGE2, 120 minutes) that maximize the activation of the prostaglandin pathway by dmPGE2 in human CD34+ cells. Isolated human CD34+ from umbilical cord blood were incubated ex vivo in Stem Span media with 10uM 16,16-dmPGE2 or DMSO. Two treatment conditions were evaluated (4 deg C for 1 hour, 37 deg C for 2 hours) with either 3 or 7 biological replicates at each condition. Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.
2012-04-15 | E-GEOD-36547 | biostudies-arrayexpress
Project description:Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the “effective dose” of HSCs. Molecular profiling with Affymetrix GeneChips were used to determine the optimal ex vivo modulation conditions (e.g., temperature and media) for use in a clinical setting by measured pathway induced expression changes. Isolated human CD34+ from umbilical cord blood were incubated ex vivo in Stem Span (SS) media evaluating three treatment temperatures (4 deg C, 25 deg C, and 37 deg C) with 10uM 16,16-dmPGE2 or Vehicle (DMSO) for 2 hours. To evaluate optimal media, similar CD34+ cells were incubated ex vivo in either Stem Span-SFEM (SS) media or 8% Low Molecular Weigh Dextran 40/5% HSA solution (LMD/HSA) with 10uM 16,16-dmPGE2 or Vehicle (DMSO) for 2 hours at 37 deg C. Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.
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Project description:Human prostate cancer C4-2 cells treated with COH29 and DMSO. Cells were treated with DMSO, 10uM or 20 uM COH29 for 48 hours. Cells were prepared for RNA-seq.
2020-02-20 | GSE117921 | GEO
Project description:Abstract: Hematopoietic stem cells (HSCs) are used in transplantation therapy to reconstitute the hematopoietic system. Human cord blood (hCB) transplantation has emerged as an attractive alternative treatment option when traditional HSC sources are unavailable, however, the absolute number of hCB HSCs transplanted is significantly lower than bone marrow or mobilized peripheral blood stem cells (MPBSCs). We previously demonstrated that dimethyl-prostaglandin E2 (dmPGE2) increased HSCs in vertebrate models. Here, we describe preclinical analyses of the therapeutic potential of dmPGE2-treatment using human and non-human primate HSCs. dmPGE2 significantly increased total human hematopoietic colony formation in vitro and enhanced engraftment of unfractionated and CD34+ hCB following xenotransplantation. In non-human primate autologous transplantation, dmPGE2-treated CD34+ MPBSCs showed stable multilineage engraftment over one year post-infusion. Together, our analyses indicated that dmPGE2 mediates conserved responses in HSCs from human and non-human primates, and provided sufficient preclinical information to support proceeding to an FDA-approved phase 1 clinical trial. In order to identify the potential mechanism of action of dmPGE2 on gene expression and HSC function, and to possibly explain the muted response of rhesus CD34+ MPBSCs to dmPGE2 exposure, microarray gene expression analysis was conducted. Human and rhesus CD34+ MPBSCs were exposed to DMSO control or dmPGE2 at a dose of either 10 and 50 uM as described above, and processed for microarray analysis at 0, 2, 6, 12 and 24 hours post treatment. Four human donors contributed 8 to 10 samples each at varying time points and dosage for a total of 37 samples (2 samples were technical repeats). Six rhesus macaques contributed 3 to 9 samples each at varying time points and dosage for a total of 28 samples (4 samples were technical repeats). Pooled PBMC's from 6 donors aphereses were used as a reference sample.
2012-06-24 | E-GEOD-27126 | biostudies-arrayexpress
Project description:Patients with autoimmune disorders exhibit highly reproducible gene expression profiles in their peripheral blood mononuclear cells. These signatures may result from chronic inflammation, other disease manifestations, or may reflect family resemblance. To test the latter hypothesis, we determined gene expression profiles in unaffected first-degree relatives of individuals with autoimmune disease. Gene expression profiles in unaffected first-degree relatives resembled the profiles found in individuals with autoimmune diseases. A high percentage of differentially expressed genes in unaffected first-degree relatives were previously identified as autoimmune signature genes. Examination of the linear regression relationship of gene transcript levels between parent-offspring pairs revealed that autoimmune signature genes display high levels of family resemblance. Taken together, these results support the hypothesis that these variations in gene transcript levels are associated with family resemblance rather than clinical manifestations of disease. Gene expression profiling of autoimmune families
2010-06-09 | E-GEOD-3459 | biostudies-arrayexpress
Project description:Myeloid-derived suppressor cell exosomes have significant immunoregulatory effects in autoimmune disease as exemplified in mouse alopecia areata
| PRJEB25444 | ENA
Project description:Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the "effective dose" of HSCs. Molecular profiling with Affymetrix GeneChips were used to evaluate if increasing the concentration of prostaglandin at 25 and 37 deg C could increase biological responses. Isolated human CD34+ cells from umbilical cord blood were incubated ex vivo in Stem Span (SS) media evaluating five concentrations of 16,16-dmPGE2 (0.1uM, 1uM, 10uM, 50uM, and 100uM) or Vehicle (DMSO) for 2 hours at 25 or 37 deg C. Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.
2013-09-12 | E-GEOD-48541 | biostudies-arrayexpress