Development of a potency test assay for CD34+ cell-based for acute myocardial infarction
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE220865 | GEO | 2022/12/16
REPOSITORIES: GEO
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Project description:A catalytic role has been proposed in neoplastic angiogenesis and cancer progression for bone marrow-derived endothelial progenitor cells (EPCs). However, in preclinical and clinical studies the quantitative role of marrow-derived EPCs in cancer vascularization was found to be extremely variable. Adipose tissue represents an attractive source of autologous adult stem cells due to its abundance and surgical accessibility. CD34+cells from Lipotransfer aspirates (LAs) of patients undergoing breast reconstruction after breast cancer surgery were compared with CD34+ cells from Leucapheresis of normal subjects. Two samples of purified CD34+ cells from Lipotransfer Aspirates (LAs) were compared with two samples of CD34+ cells from Leucapheresis samples. The reference were considered the CD34+ RNA from leucapheresis
2011-08-15 | E-GEOD-31415 | biostudies-arrayexpress
Project description:A catalytic role has been proposed in neoplastic angiogenesis and cancer progression for bone marrow-derived endothelial progenitor cells (EPCs). However, in preclinical and clinical studies the quantitative role of marrow-derived EPCs in cancer vascularization was found to be extremely variable. Adipose tissue represents an attractive source of autologous adult stem cells due to its abundance and surgical accessibility. CD34+cells from Lipotransfer aspirates (LAs) of patients undergoing breast reconstruction after breast cancer surgery were compared with CD34+ cells from Leucapheresis of normal subjects.
2011-08-16 | GSE31415 | GEO
Project description:Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) is a potential treatment for patients suffering from aggressive multiple sclerosis (MS). However it remains unresolved whether autologous CD34+ hematopoietic progenitor cells of MS patients show gene expression differences prior to aHSCT that indicate a preset proinflammatory state, which would then also predispose to or predetermine recurrence of the autoimmune disease. To approach this key point we compared the micro RNA gene expression signature of CD34+ cells collected from MS patients and healthy donors (HD). Gene expression of CD34+ cells was analysed with the Human miRNA Microarray (Agilent-Technologies) chip. No substantial alterations in the gene expression profile of CD34+ HPCs in MS were observed.
2012-09-05 | GSE27690 | GEO
Project description:The label-free quantitative proteome was generated for 42 primary AML patient samples enriched for CD34+ cells (or mononuclear cells in the case of NPMcyt sameples) and as controls 6 mobilized peripheral blood CD34+ cells were included. Furthermore, 6 AML cell lines were included, and also primary mesenchymal stem cells grown under normaoxia or hypoxia were included.
2022-03-15 | PXD030463 | Pride
Project description:Rationale: Pro-angiogenic effects of mobilised bone-marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. MicroRNAs (miRNA/miR) are key regulators of angiogenesis. Objective: To determine the differential regulation of angiomiRs, i.e microRNAs regulating neovascularisation, in mobilised CD34+ progenitor cells obtained from patients with an acute ST-segment elevation myocardial infarction (STEMI) as compared to those with stable coronary artery disease (sCAD) or healthy subjects. Methods and Results: CD34+ progenitor cells were isolated from patients with STEMI (on day 0 and day 5), sCAD and healthy subjects (n=27). CD34+ progenitor cells of patients with STEMI exhibited increased pro-angiogenic activity as compared to CD34+ cells from the other groups. Using a PCR-based miRNA-array and Real-Time PCR validation we identified a profound up-regulation of two known angio-miRs, i.e. miR-378 and let-7b, in CD34+ cells of patients with STEMI. Especially, we demonstrate that miR-378 is a critical regulator of the pro-angiogenic capacity of CD34+ progenitor cells and its stimulatory effects on endothelial cells in-vitro and in-vivo, whereas let-7b up-regulation in CD34+ cells failed to proof its effect on endothelial cells in-vivo. Conclusion: The present study demonstrates for the first time a significant upregulation of the angiomiRs miR-378 and let-7b in mobilised CD34+ progenitor cells of patients with STEMI. The increased pro-angiogenic activity of these cells in patients with STEMI and the observation that in particular miR-378 regulates the angiogenic capacity of CD34+ progenitor cells in-vivo suggest that this unique microRNA expression pattern represents a novel endogenous repair mechanism activated in acute myocardial infarction.
2016-11-11 | GSE53211 | GEO
Project description:Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) is a potential treatment for patients suffering from aggressive multiple sclerosis (MS). However it remains unresolved whether autologous CD34+ hematopoietic progenitor cells of MS patients show gene expression differences prior to aHSCT that indicate a preset proinflammatory state, which would then also predispose to or predetermine recurrence of the autoimmune disease. To approach this key point we compared the gene expression signature of CD34+ and CD34- cells collected from MS patients and healthy donors (HD). Whole genome gene expression of CD34+ and CD34- cells was analysed with the Human 4x44K Design Array (Agilent-Technologies). As main observation we found only minor differences in the gene expression signature of MS patients compared to HD. Only a single gene, troponin-type-1 (TNNT1), reached statistical significance after correction for multiple comparisons (logFC=3.1, p<0.01). There was a decreased expression of several protease genes, myeloperoxidase (MPO), neutrophil-elastase (ELA2), cathepsin-G (CTSG) and serine-protease 21 (PRSS21) in HPCs of MS patients, albeit not reaching statistical significance. In summary we did not detect substantial alterations in the gene expression profile of CD34+ HPCs in MS. Our data support the use of autologous hematopoietic stem cell transplantation for treatment of an autoimmune disease.
2012-09-05 | GSE27688 | GEO
Project description:Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) is a potential treatment for patients suffering from aggressive multiple sclerosis (MS). However it remains unresolved whether autologous CD34+ hematopoietic progenitor cells of MS patients show gene expression differences prior to aHSCT that indicate a preset proinflammatory state, which would then also predispose to or predetermine recurrence of the autoimmune disease. To approach this key point we compared the gene expression signature of CD34+ and CD34- cells collected from MS patients and healthy donors (HD). Whole genome gene expression of CD34+ and CD34- cells was analysed with the Human 4x44K Design Array (Agilent-Technologies). As main observation we found only minor differences in the gene expression signature of MS patients compared to HD. Only a single gene, troponin-type-1 (TNNT1), reached statistical significance after correction for multiple comparisons (logFC=3.1, p<0.01). There was a decreased expression of several protease genes, myeloperoxidase (MPO), neutrophil-elastase (ELA2), cathepsin-G (CTSG) and serine-protease 21 (PRSS21) in HPCs of MS patients, albeit not reaching statistical significance. In summary we did not detect substantial alterations in the gene expression profile of CD34+ HPCs in MS. Our data support the use of autologous hematopoietic stem cell transplantation for treatment of an autoimmune disease. Samples of CD34+ cells were obtained from 4 female MS patients and 4 age matched healthy donors (3 female) mobilized by G-CSF (2x5M-NM-<g/kg/day) and 4 MS patients (2 female) mobilized by G-CSF (5M-NM-<g/kg/day) plus Cyclophosphamide (Cy, 4g/m2). White blood cells, containing the CD34+ cell fraction, were collected by leucocytapheresis from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and processed at one center and CD34+ HPCs purified by magnetic bead separation using the autoMACS system (Miltenyi). Purity and viability of CD34+ cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human 4x44K Design Array (Agilent-Technologies).
2012-09-05 | E-GEOD-27688 | biostudies-arrayexpress
Project description:Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) is a potential treatment for patients suffering from aggressive multiple sclerosis (MS). However it remains unresolved whether autologous CD34+ hematopoietic progenitor cells of MS patients show gene expression differences prior to aHSCT that indicate a preset proinflammatory state, which would then also predispose to or predetermine recurrence of the autoimmune disease. To approach this key point we compared the micro RNA gene expression signature of CD34+ cells collected from MS patients and healthy donors (HD). Gene expression of CD34+ cells was analysed with the Human miRNA Microarray (Agilent-Technologies) chip. No substantial alterations in the gene expression profile of CD34+ HPCs in MS were observed. Samples of CD34+ cells were obtained from 4 female MS patients and 4 age matched healthy donors (3 female) mobilized by G-CSF (2x5μg/kg/day). White blood cells, containing the CD34+ cell fraction, were collected by leucocytapheresis from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and processed at one center and CD34+ HPCs purified by magnetic bead separation using the autoMACS system (Miltenyi). Purity and viability of CD34+ cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human miRNA Microarray (Agilent-Technologies).
2012-09-05 | E-GEOD-27690 | biostudies-arrayexpress
Project description:ImportanceEmergency department (ED) investigations of patients with suspected acute myocardial infarction (AMI) are time consuming, partly because of the turnaround time of laboratory tests. Current point-of-care troponin assays shorten test turnaround times but lack precision at lower concentrations. Development of point-of-care troponin assays with greater analytical precision could reduce the decision-making time in EDs for ruling out AMI.ObjectiveTo determine the clinical accuracy for AMI of a single troponin concentration measured on arrival to ED with a new-generation, higher precision point-of-care assay with a 15-minute turnaround time.Design, setting, and participantsThis observational study occurred at a single urban regional ED. Adults presenting acutely from the community to the ED with symptoms suggestive of AMI were included. Troponin concentrations were measured on ED arrival with both a novel point-of-care assay (i-STAT TnI-Nx; Abbott Point of Care) and a high-sensitivity troponin I assay (Architect hs-cTnI; Abbott Diagnostics).Main outcomes and measuresThe primary outcome was type 1 AMI during index presentation. We compared the discrimination ability of the TnI-Nx assay with the hs-cTnI assay using the area under receiver operator characteristic curve (AUC) and sensitivity, negative predictive value, and the proportion of negative test results at thresholds with 100% sensitivity.ResultsOf 354 patients (255 [72.0%] men; mean [SD] age, 62 [12] years), 57 (16.1%) experienced an AMI. Eighty-five patients (24.0%) presented to the ED less than 3 hours after symptom onset. No difference was found between the AUC of the TnI-Nx assay (0.975 [95% CI, 0.958-0.993]) and the hs-cTnI assay (0.970 [95% CI, 0.949 to 0.990]; P = .46). A TnI-Nx assay result of less than 11 ng/L identified 201 patients (56.7%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 98.2%-100%). In comparison, an hs-cTnI assay result of less than 3 ng/L identified 154 patients (43.5%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 97.6%-100%).Conclusions and relevanceA novel point-of-care troponin assay that can produce a result 15 minutes after blood sampling had comparable discrimination ability to an hs-cTnI assay for ruling out AMI after a single blood test. Use in the ED may facilitate earlier decision making and could expedite the safe discharge of a large proportion of low-risk patients.
| S-EPMC6583693 | biostudies-literature
Project description:Ischemic cardiovascular disease represents one of the largest epidemics currently facing the aging population. Current literature has illustrated the efficacy of autologous, stem cell therapies as novel strategies for treating these disorders. The CD34+ hematopoetic stem cell has shown significant promise in addressing myocardial ischemia by promoting angiogenesis that helps preserve the functionality of ischemic myocardium. Unfortunately, both viability and angiogenic quality of autologous CD34+ cells decline with advanced age and diminished cardiovascular health.To offset age- and health-related angiogenic declines in CD34+ cells, we explored whether the therapeutic efficacy of human CD34+ cells could be enhanced by augmenting their secretion of the known angiogenic factor, sonic hedgehog (Shh).When injected into the border zone of mice after acute myocardial infarction, Shh-modified CD34+ cells (CD34(Shh)) protected against ventricular dilation and cardiac functional declines associated with acute myocardial infarction. Treatment with CD34(Shh) also reduced infarct size and increased border zone capillary density compared with unmodified CD34 cells or cells transfected with the empty vector. CD34(Shh) primarily store and secrete Shh protein in exosomes and this storage process appears to be cell-type specific. In vitro analysis of exosomes derived from CD34(Shh) revealed that (1) exosomes transfer Shh protein to other cell types, and (2) exosomal transfer of functional Shh elicits induction of the canonical Shh signaling pathway in recipient cells.Exosome-mediated delivery of Shh to ischemic myocardium represents a major mechanism explaining the observed preservation of cardiac function in mice treated with CD34(Shh) cells.
| S-EPMC3511820 | biostudies-literature