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Angelo Avogaro - One of the best experts on this subject based on the ideXlab platform.

  • long term prediction of cardiovascular outcomes by circulating cd34 and cd34 cd133 stem cells in patients with type 2 diabetes
    Diabetes Care, 2017
    Co-Authors: Gian Paolo Fadini, Mauro Rigato, Roberta Cappellari, Benedetta Maria Bonora, Angelo Avogaro
    Abstract:

    OBJECTIVE Cardiovascular risk varies substantially in the population with diabetes, and biomarkers can improve risk stratification. Circulating stem cells predict future cardiovascular events and death, but data for the population with diabetes are scant. In this study we evaluated the ability of circulating stem cell levels to predict future cardiovascular outcomes and improve risk discrimination in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A cohort of 187 patients with type 2 diabetes was monitored for a median of 6.1 years. The primary outcome was time to a first cardiovascular event, defined as 3-point major adverse cardiovascular event (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) plus hospitalization for cardiovascular causes. At baseline, we measured six stem/progenitor cell phenotypes in peripheral blood based on expression of CD34, CD133, and KDR. RESULTS The primary outcome occurred in 48 patients (4.5/100 patient-years). Patients with incident cardiovascular events had significantly lower CD34+ and CD34+CD133+ cells than those without. Higher rates of cardiovascular events occurred in patients with below median levels of CD34+ and CD34+CD133+. In Cox proportional hazards regression analyses, a reduced CD34+ (hazard ratio 2.21 [95% CI 1.14–4.29]) and CD34+CD133+ (2.98 [1.46–6.08]) cell count independently predicted future events. Addition of the CD34+ cell count to the reference model or the UK Prospective Diabetes Study risk engine improved C statistics, continuous net reclassification improvement, and/or integrated discrimination index. CONCLUSIONS In patients with type 2 diabetes, a reduced baseline level of circulating CD34+ stem cells predicts adverse cardiovascular outcomes up to 6 years later and improves risk stratification.

  • acute effects of linagliptin on progenitor cells monocyte phenotypes and soluble mediators in type 2 diabetes
    The Journal of Clinical Endocrinology and Metabolism, 2016
    Co-Authors: Gian Paolo Fadini, Roberta Cappellari, Benedetta Maria Bonora, Lisa Menegazzo, Monica Vedovato, Elisabetta Iori, Maria Cristina Marescotti, Mattia Albiero, Angelo Avogaro
    Abstract:

    Context: Circulating cells, including endothelial progenitor cells (EPCs) and monocyte subtypes, are involved in diabetic complications. Modulation of these cells may mediate additional benefits of glucose-lowering medications. Objective: We assessed whether the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin acutely modifies EPCs and monocyte subsets in patients with type 2 diabetes. Design: This was a randomized, crossover, placebo-controlled trial. Setting: The study was conducted at a tertiary referral diabetes outpatient clinic. Patients: Forty-six type 2 diabetes patients with (n = 18) or without (n = 28) chronic kidney disease (CKD) participated in the study. Intervention: Intervention included a 4-day treatment with linagliptin 5 mg or placebo during two arms separated by a 2-week washout. Main Outcome Measures: Before and after each treatment, we determined the levels of circulating progenitor cells (CD34, CD133, KDR) and monocyte subtypes (CD14/CD16, chemokine and scavenger receptors) and t...

  • circulating cd34 cells metabolic syndrome and cardiovascular risk
    European Heart Journal, 2006
    Co-Authors: Gian Paolo Fadini, Saula Vigili De Kreutzenberg, Anna Coracina, Ilenia Baesso, Carlo Agostini, A Tiengo, Angelo Avogaro
    Abstract:

    Aims Circulating progenitor cells are believed to participate in cardiovascular (CV) homeostasis and their exhaustion has been linked to CV damage. As general agreement on their characterization is lacking, this work was carried out to assess the relationships between different antigenic profiles of progenitor cells and CV risk, with special regard to metabolic syndrome (MetSyn). Methods and results CD34, CD133, and KDR were used to quantify circulating progenitors in 214 subjects at different levels of CV risk. In a cross-analysis of six different cell subtypes (CD34+, CD133+, CD34+CD133+, CD34+KDR+, CD133+KDR+, and CD34+CD133+KDR+), CD34+ progenitors showed the best correlation with CV parameters and risk estimates. Components of the MetSyn were all characterized by reduction of CD34+ cells and acted synergistically in decreasing CD34+ cell count. Moreover, CD34+ cell count demonstrated a high performance in detecting high CV risk. Conclusion These data demonstrate that CD34 identifies progenitor cells linked to CV risk, showing a close negative correlation between CD34+ cells and CV risk, as well as a synergic detrimental effect of clustered metabolic components. Progenitor cell count may be used as a surrogate marker of CV risk, whereas extensive antigenic characterization may not be useful for this purpose.

Kazunari Kaneko - One of the best experts on this subject based on the ideXlab platform.

  • cd133 is a positive marker for a distinct class of primitive human cord blood derived cd34 negative hematopoietic stem cells
    Leukemia, 2014
    Co-Authors: Masaya Takahashi, Yoshikazu Matsuoka, Keisuke Sumide, Ryusuke Nakatsuka, Tatsuya Fujioka, Hirao Kohno, Yutaka Sasaki, K Matsui, Hiroaki Asano, Kazunari Kaneko
    Abstract:

    The identification of human CD34-negative (CD34−) hematopoietic stem cells (HSCs) provides a new concept for the hierarchy in the human HSC compartment. Previous studies demonstrated that CD34− severe combined immunodeficiency (SCID)-repopulating cells (SRCs) are a distinct class of primitive HSCs in comparison to the well-characterized CD34+CD38− SRCs. However, the purification level of rare CD34− SRCs in 18 lineage marker-negative (Lin−) CD34− cells (1/1000) is still very low compared with that of CD34+CD38− SRCs (1/40). As in the mouse, it will be necessary to identify useful positive markers for a high degree of purification of rare human CD34− SRCs. Using 18Lin−CD34− cells, we analyzed the expression of candidate positive markers by flow cytometric analysis. We finally identified CD133 as a reliable positive marker of human CB-derived CD34− SRCs and succeeded in highly purifying primitive human CD34− HSCs. The limiting dilution analysis demonstrated that the incidence of CD34− SRCs in 18Lin−CD34−CD133+ cells was 1/142, which is the highest level of purification of these unique CD34− HSCs to date. Furthermore, CD133 expression clearly segregated the SRC activities of 18Lin−CD34− cells, as well as 18Lin−CD34+ cells, in their positive fractions, indicating its functional significance as a common cell surface maker to isolate effectively both CD34+ and CD34− SRCs.

Jianzhu Chen - One of the best experts on this subject based on the ideXlab platform.

  • human cd34 cd133 hematopoietic stem cells cultured with growth factors including angptl5 efficiently engraft adult nod scid il2rγ nsg mice
    PLOS ONE, 2011
    Co-Authors: Adam Drake, Maroun Khoury, Ilya B Leskov, Bettina P Iliopoulou, Maria F Fragoso, Harvey F Lodish, Jianzhu Chen
    Abstract:

    Increasing demand for human hematopoietic stem cells (HSCs) in clinical and research applications necessitates expansion of HSCs in vitro. Before these cells can be used they must be carefully evaluated to assess their stem cell activity. Here, we expanded cord blood CD34+ CD133+ cells in a defined medium containing angiopoietin like 5 and insulin-like growth factor binding protein 2 and evaluated the cells for stem cell activity in NOD-SCID Il2rg−/− (NSG) mice by multi-lineage engraftment, long term reconstitution, limiting dilution and serial reconstitution. The phenotype of expanded cells was characterized by flow cytometry during the course of expansion and following engraftment in mice. We show that the SCID repopulating activity resides in the CD34+ CD133+ fraction of expanded cells and that CD34+ CD133+ cell number correlates with SCID repopulating activity before and after culture. The expanded cells mediate long-term hematopoiesis and serial reconstitution in NSG mice. Furthermore, they efficiently reconstitute not only neonate but also adult NSG recipients, generating human blood cell populations similar to those reported in mice reconstituted with uncultured human HSCs. These findings suggest an expansion of long term HSCs in our culture and show that expression of CD34 and CD133 serves as a marker for HSC activity in human cord blood cell cultures. The ability to expand human HSCs in vitro should facilitate clinical use of HSCs and large-scale construction of humanized mice from the same donor for research applications.

Diane S Krause - One of the best experts on this subject based on the ideXlab platform.

  • cotransplantation of human mesenchymal stem cells enhances human myelopoiesis and megakaryocytopoiesis in nod scid mice
    Experimental Hematology, 2003
    Co-Authors: Maria K Angelopoulou, Enrico M Novelli, Joanna E Grove, Henry M Rinder, Curt I Civin, Linzhao Cheng, Diane S Krause
    Abstract:

    Objective. For approximately 5% of autologous transplant recipients and a higher proportion of allogeneic transplant recipients, low level and delayed platelet engraftment is an ongoing problem. Mesenchymal stem cells (MSC), which can be derived from bone marrow as well as other organs, are capable of differentiation into multiple cell types and also support hematopoiesis in vitro. Because cotransplantation of marrow-derived stromal cells has been shown to enhance engraftment of human hematopoietic stem cells, we hypothesized that cotransplantation of MSC could enhance platelet and myeloid cell development. Materials and Methods. We tested this hypothesis by transplantation of CD34-selected mobilized human peripheral blood stem cells (PBSC) into sublethally irradiated NOD/SCID mice with or without culture-expanded human MSC and evaluated human myeloid, lymphoid, and megakaryocytic engraftment with flow cytometry and in vitro cultures. Results. WefindthatMSCcotransplantationenhances humancellengraftmentwhenalimiting dose (1 × 10 6 ) of CD34 cells is administered. This enhancement is characterized by a shift in the differentiation of human cells from predominantly B lymphocytes to predominantly CD13, CD14, and CD33 myeloid cells with a corresponding increase in myeloid CFU in the marrow. Megakaryocytopoiesis is enhanced by MSC cotransplantation as assessed by an increase in both marrow CFU-MK and circulating human platelets. In contrast, MSC do not affect the percentage of human bone marrow cells that expresses CD34. Conclusions. Cotransplantation of human mesenchymal stem cells with CD34-selected hematopoietic stem cells enhances myelopoiesis and megakaryocytopoiesis. 2003 International Society for Experimental Hematology. Published by Elsevier Science Inc.

Dennis E. Van Epps - One of the best experts on this subject based on the ideXlab platform.

  • phenotypic analysis and characterization of cd34 cells from normal human bone marrow cord blood peripheral blood and mobilized peripheral blood from patients undergoing autologous stem cell transplantation
    Clinical Immunology and Immunopathology, 1994
    Co-Authors: James G. Bender, S F Williams, Kristen L Unverzagt, D. E. Walker, Stephen D Smith, Dennis E. Van Epps
    Abstract:

    Abstract Single- and multicolor flow cytometry were used to define progenitor subsets in normal human bone marrow and peripheral blood, cord blood, and blood following mobilization of CD34+ progenitor cells by cyclophosphamide or cyclophosphamide/etoposide/G-CSF treatment. CD34 cells were quantitated and subsets of CD34+ cells were defined by coexpression of CD33, CD13, CD10, CD19, CD45RA, and CD71. Myeloid and erythroid progenitors were quantitated by sorting single CD34+ cells into individual wells of 96-well plates containing methylcellulose, IL-3, GM-CSF, G-CSF, IL-6, and erythropoietin. Comparative studies of CD34 cells showed that the percentage of CD34+ mononuclear cells was greatest in blood samples from patients following mobilization treatment with cyclophosphamide/etoposide/G-CSF averaging 2%. By comparison, the remaining sample groups ranged from 1.68 to 0.15% CD34 cells in this order, bone marrow > cord blood > cyclophosphamide mobilized blood > peripheral blood. Comparison of CD34 cells per milliliter of bone marrow or blood showed a range of 22.4 × 104 to 0.65 × 104/ml in the following order, bone marrow > chemotherapy/etoposide/G-CSF > cord blood > cyclophosphamidemobilized blood. Comparative analysis of CD34 subsets from different sources showed significant differences, particularly bone marrow and blood samples. A distinct population of CD34+ CD19+ (Leu 12) CD10+ (CALLA) pre-B lymphocyte cells was defined in bone marrow with lower side and forward light scatter characteristics and was variable between donors (29.8 ± 16.9%, mean ± 1 SD; range, 3-54%; n = 8). This population was not found to a significant degree in blood and also expressed CD45RA (Leu 18). Coexpression studies of CD45RA and CD71 (transferrin receptor) expression on CD34+ cells defined a CD45RA-CD71+ population containing 89 ± 6.3% (n = 4) BFU-E and a CD45RA+CD71+ population that contained all CFU-GM (n = 4). LeuM7 (CD13) stained a larger percentage to a greater intensity than MY7 (CD13). Coexpression of CD45RA (Leu 18) and CD13 (LeuM7) defined a subset of CD13+ CD45RA+ cells enriched for CFU-GM and CFU-M with a cloning efficiency of 31%. Coexpression of CD33 (MY9) and CD13 (MY7) defined a population that was predominantly CFU-GM with a cloning efficiency of 38%. These studies define CD34+ phenotypes containing pure populations of B lymphocyte, granulocyte-macrophage, or erythroid progenitors and demonstrate the utility of multiparameter flow cytometry to define lineage-committed CD34+ cells.

  • characterization of chemotherapy mobilized peripheral blood progenitor cells for use in autologous stem cell transplantation
    Bone Marrow Transplantation, 1992
    Co-Authors: James G. Bender, S F Williams, Sage R Myers, D Nottleman, Kristen L Unverzagt, L B To, D. E. Walker, Dennis E. Van Epps
    Abstract:

    : Twenty patients were treated with chemotherapy to mobilize progenitors into the blood. Peripheral blood stem cells were quantitated in peripheral blood or leukapheresis products using colony assays and flow cytometric measurement of CD34+ cells. In four patients where complete sets of serial samples were obtained, the appearance of CD34+ cells preceded the increase in CFU-GM by 24-48 h. Peak levels of CD34+ cells ranged from 0.6-5% and coincided with the peak increase in CFU-GM. Mobilized CD34+ cells contained subsets expressing CD33, CD13, CD45RA, CD38, HLA-DR, CD61 and CD41. Subsets of CD34+ cells expressing CD33, CD13, or CD45RA represent committed myeloid progenitors. In contrast to bone marrow CD34+ cells, few mobilized CD34+ cells expressed CD71, CD7, CD19 or CD10. Prompt engraftment of granulocytes greater than 500 x 10(6)/l at a median of 13 days and platelets greater than 50 x 10(9)/l at a median of 15 days was observed in patients reconstituted with mobilized cells. These data indicate that CD34+ cells mobilized during recovery from chemotherapy are predominantly myeloid in phenotype and contain few actively proliferating cells or cells with lymphoid phenotypes.