Abstract 697: Mobilization of Oct-4 + Bone Marrow-Derived Very Small Embryonic-Like Stem Cells in Patients with Acute Myocardial Infarction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Wojciech Wojakowski ◽  
Magda Kucia ◽  
Boguslaw Machalinski ◽  
Edyta Paczkowska ◽  
Joanna Ciosek ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Pluripotent Stem Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Small Cells ◽  
Acute Mi

Bone marrow-derived CD34 + CXCR4 + progenitor cells are mobilized into peripheral blood early in acute myocardial infarction (MI). Adult murine bone marrow contains population of small CD34 + lin − CD45 − CXCR4 + cells expressing markers of pluripotent stem cells (PSC) SSEA, Oct-4 and Nanog. This population of very small embryonic-like cells (VSEL) has unique morphology (small size 2– 4 μm, large nucleus, euchromatin) and capability to form embrioid bodies (EB). Murine EB-derived cells can in vitro differentiate into cells from all three germ layers including cardiomyocytes. We hypothesized that in patients with acute MI small cells expressing the VSEL immunophenotype and PSC markers are present in bone marrow and mobilized into peripheral blood. Blood samples (20 mL) from 18 patients with acute MI were obtained after 12 hours, 2 and 5 days after symptoms onset. Bone marrow samples (20 mL) were obtained from 2 patients with acute MI and 3 healthy volunteers. Mononuclear cells were isolated using hypotonic lysis and samples were analyzed by FACS. Mobilization of following cell populations was confirmed: hematopoietic lin − CD45 + CXCR4 + , lin − CD45 + CD133 + , lin − CD45 + CD34 + and non-hematopoietic (VSEL) lin − CD45 − CXCR4 + , lin − CD45 − CD133 + , lin − CD45 − CD34 + . Analysis of the cell number using lymphocyte gate showed more significant increase of CD45 + (hematopoietic) populations of lin − CD34 + , lin − CD133 + and lin − CXCR4 + cells. After gating for small events (VSEL size range) we found more significant mobilization of small, non-hematopoietic populations of lin − CD34 + , lin − CD133 + and lin − CXCR4 + cells (Table ). The expression of PSC markers (Oct-4, Nanog, SSEA-1) in VSEL was confirmed using real-time RT-PCR. Conclusion: We report for the first time that acute MI is associated with mobilization of non-hematopoietic VSELs expressing pluripotent stem cells markers.

scholarly journals Increase in circulating stem cells following chemotherapy in man

Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 1031-1039 ◽  
Author(s):  
CM Richman ◽  
RS Weiner ◽  
RA Yankee
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Intensive Chemotherapy ◽  
Large Numbers ◽  
Intermittent Chemotherapy

Abstract The number of circulating granulocytic stem cells (CFU-C) was determined by the in vitro methylcellulose technique in cancer patients receiving intermittent chemotherapy. In 17 patients studied prior to therapy, the median CFU-C concentration per 2 X 10(5) mononuclear cells plated was six, compared to a posttreatment median of 23 in 21 patients (p less than 0.001). Large numbers of stem cells were obtained by leukopheresis and cryopreserved with a 99.5% median CFU-C recovery. Cyclical changes in the concentration of stem cells with maximum values of 20 times baseline were demonstrated in a patient studied at weekly intervals during multiple courses of treatment. It was estimated that, at peak CFU-C concentrations, a quantity of stem cells equivalent to that present in a bulk bone marrow harvest could be obtained from the peripheral blood by a 17-liter pheresis. These results suggest that it may be practical to obtain an adequate number of stem cells from the peripheral blood to study autologous stem cell infusion as a means of averting myelosuppression in patients receiving intensive chemotherapy.

Implantation of Autologous Bone Marrow Mononuclear Cells in Patients after Acute Myocardial Infarction Via Coronary Artery.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4220-4220
Author(s):  
Martin Klabusay ◽  
Milan Navratil ◽  
Zdenek Koristek ◽  
Ladislav Groch ◽  
Jaroslav Meluzin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Coronary Artery ◽  
Adult Stem Cells ◽  
Mononuclear Cells ◽  
Cellular Therapy ◽  
Bone Marrow Cells ◽  
Heart Function

Abstract Background: Several populations of adult stem cells have been identified in bone marrow: hematopoietic stem cells, which are able to regenerate hematopoiesis in all of its lineages, mesenchymal stem cells, which can give rise to connective tissues (bone, cartilage and fat), and endothelial progenitor cells, which can initiate angiogenesis. Adult stem cells are found within the mononuclear cells compartment of bone marrow. Recent reports describe the effect of mononuclear bone marrow cells in reparation of ischemic tissue damage. Methods: The authors designed the experimental protocol of cellular therapy for patients after acute myocardial infarction. Inclusion criteria were: first myocardial infarction treated with primary angioplasty and stent implantation, confirmed non-viability of myocardium by USG, PET and SPECT, elevated CK-MB, and age below 70 years. Patients with intervention on other coronary artery, in unstable condition at day 4 through 6, and with serious non-cardiac disease were excluded. Patients undergoing coronary angioplasty, who signed informed consent, were randomized into three arms: A - high dose of 1•108 mononuclear cells, B - low dose of 1•107 cells, C - no cells. The autologous bone marrow was collected within day 7 after infarction. The mononuclear cells were separated, cultured for 24 hours in serum-free medium, and implanted through catheter via coronary artery into the damaged heart muscle in 7 subsequent injections. Mononuclear cells were analyzed with multicolor flow cytometry and culture assays of CFU-GM and CFU-Meg. The cardiac perfusion, metabolism and function were evaluated with SPECT, PET and echocardiography at 3 months after cell implantation. Results: 31 patients enrolled into the study underwent the protocol (9 in group A, 11 in groups B and C, respectively), and their cardiac functions were evaluated afterwards. There were no serious adverse effects of cell therapy procedure observed in each group. The analysis at 3 months interval showed an improvement in metabolism in the cellular therapy arms detected by PET. Left ventricle ejection fraction improved from 38 to 44%, although this improvement in global heart function was not statistically significant. However, regional heart function at the infarction site (peak systolic velocity of the infarcted wall) improved from 4.1 to 5.0 cm/s in the arm A (p<0.01), while no improvement was observed in arms B and C. A very significant improvement in metabolism and regional function of infarcted area of left ventricle was observed in three patients, all within the treatment arm A. Conclusion: Mononuclear bone marrow cells as a potential source of adult stem cells can be enriched, cultured ex vivo, and safely used in the cellular therapy protocols for ischemic heart disease. The functional benefit of dose of 1•108 mononuclear cells can be detected in a group of patients after acute myocardial infarction.

scholarly journals MYOCARDIAL PERFUSION AFTER INTRACORONARY INFUSION OF MONONUCLEAR CELLS OF BONE MARROW OR PERIPHERAL BLOOD AFTER ACUTE MYOCARDIAL INFARCTION

2010 ◽  
Vol 55 (10) ◽  
pp. A110.E1024 ◽  
Author(s):  
Farshid Afsharzada ◽  
Robin Nijveldt ◽  
Alexander Hirsch ◽  
Pieter A van der Vleuten ◽  
Aernout M. Beek ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Bone Marrow ◽  
Myocardial Perfusion ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Intracoronary Infusion

scholarly journals Increase in circulating stem cells following chemotherapy in man

Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 1031-1039 ◽  
Author(s):  
CM Richman ◽  
RS Weiner ◽  
RA Yankee
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Intensive Chemotherapy ◽  
Large Numbers ◽  
Intermittent Chemotherapy

The number of circulating granulocytic stem cells (CFU-C) was determined by the in vitro methylcellulose technique in cancer patients receiving intermittent chemotherapy. In 17 patients studied prior to therapy, the median CFU-C concentration per 2 X 10(5) mononuclear cells plated was six, compared to a posttreatment median of 23 in 21 patients (p less than 0.001). Large numbers of stem cells were obtained by leukopheresis and cryopreserved with a 99.5% median CFU-C recovery. Cyclical changes in the concentration of stem cells with maximum values of 20 times baseline were demonstrated in a patient studied at weekly intervals during multiple courses of treatment. It was estimated that, at peak CFU-C concentrations, a quantity of stem cells equivalent to that present in a bulk bone marrow harvest could be obtained from the peripheral blood by a 17-liter pheresis. These results suggest that it may be practical to obtain an adequate number of stem cells from the peripheral blood to study autologous stem cell infusion as a means of averting myelosuppression in patients receiving intensive chemotherapy.

scholarly journals Increased concentrations of bone marrow-derived stem cells in peripheral blood after acute myocardial infarction

2003 ◽  
Vol 41 (6) ◽  
pp. 400
Author(s):  
Antonio Maria Leone ◽  
Sergio Rutella ◽  
Felicita Andreotti ◽  
Luca Pierelli ◽  
Mariaelena Lombardi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Peripheral Blood

Mobilization of Human Hemopoietic Progenitor Stem Cell Via Modulating CXCR4/SDF-1 Using Galactofucan Sulfate.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1971-1971
Author(s):  
Mohammad R. Irhimeh ◽  
Ray M. Lowenthal ◽  
J. Helen Fitton
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Autologous Transplantation ◽  
White Blood Cells ◽  
Healthy Human ◽  
Cytokine Analysis ◽  
Ifn Γ

Abstract Mobilization of peripheral blood progenitor cells for hematopoietic rescue following autologous transplantation is usually achieved with the chemokine G-CSF. Engraftment potential is increased when higher levels of the receptor CXCR4 are noted on the hematopoietic progenitor stem cells (HPCs). It was previously reported that intravenous treatment with fucoidan or dextran sulfate, which are sulfated high molecular weight compounds, increased numbers of circulating mature white blood cells and HPCs in mice and nonhuman primates. This treatment also led to an increase in the pro-inflammatory cytokines IFN-γ and IL-12 levels in mice. In vitro treatment of bone marrow mononuclear cells with IFN-γ can up-regulate the expression of CXCR4 on granulocyte precursors and monocytes. We obtained ethics approval and informed consent to study the mobilization effect of orally ingested GFSTM (Galactofucan Sulfate), a seaweed-derived fucoidan, in healthy human volunteers in a single blinded placebo controlled phase I/II clinical study. Flow cytometry was used to monitor CXCR4 receptor on CD34+ stem cells. When moderate quantities (3 g/day) of seaweed containing 10% GFSTM were ingested, a slight increase in the total number of HPCs (CD34+) in the peripheral blood (PB) was observed, from 1.38 to 1.69 cells/μL (p=0.22, n=6). In addition, there was a small increase in the percentage of HPCs that expressed CXCR4 surface receptor, from 0.59 to 1.47 cells/μL, which is equivalent to 43% to 63% (p=0.19, n=6). Moreover, when 3 g/day of 75% GFSTM was ingested, a greater increase in the total number of HPCs (CD34+) in PB was observed, from 1.65 to 1.84 cells/μL (p=0.04, n=23). Furthermore, the percentage of HPCs that expressed CXCR4 increased from 0.746–1.652 cells/μL, which is equivalent to 45% to 90% (p=0.0002, n=23). Cytokine analysis, which was performed using ELISA to test for SDF-1 and IFN-γ, showed a significant increase in the plasma level of these cytokines. SDF-1 level was elevated from 1979 to 2068 pg/mL (p=0.051, n=10) and the level of IFN-γ from 9.04 to 9.90 pg/mL (p=0.007, n=10). These results suggest that GFSTM may modulate CXCR4 or disturb the SDF-1 gradient between bone marrow and PB. IFN-γ might play a role in the up-regulation of the expression of CXCR4 on CD34+ cells. To the authors’ knowledge, this is the first report of mobilization of HPCs by disruption of CXCR4/SDF-1 interaction using oral fucoidan.

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