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

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.

Abstract 12445: A Detailed Analysis of Peripheral Blood Cytokines 2-3 weeks After Acute Myocardial Infarction: IL-6-Related Impairment of Bone Marrow Function

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Mahan Shahrivari ◽  
Elizabeth Wise ◽  
Doris A Taylor ◽  
Carl J Pepine ◽  
Timothy D Henry ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Bone Marrow ◽  
Cell Therapy ◽  
Cardiac Function ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Research Network ◽  
Cytokine Levels ◽  
Cell Phenotypes

Background: Intracoronary infusion of bone marrow (BM) mononuclear cells (BM-MNCs) late after acute myocardial infarction (AMI) has shown no improvement in global or regional left ventricular (LV) function (LateTIME and SWISS-AMI). Studies in experimental AMI models suggest a possible cytokine-related depression of progenitor cell function. Furthermore, BM cell content is correlated with the LV functional response. Accordingly, we hypothesize that inflammatory cytokines associated with the late phase of AMI may impair BM function and alter progenitor cell subsets. Method: Patients with previous AMI (n=87) were recruited in a multicenter cell therapy trial by the Cardiovascular Cell Therapy Research Network (CCTRN LateTIME, NCT00684060). BM and peripheral blood (PB) were collected 2-3 weeks after AMI and examined for cell phenotypes and progenitor capacities as well as PB inflammatory and angiogenic cytokines in a core laboratory. Multiple regression analyses were conducted and correlations between cytokine levels and cell phenotypes, cell functions, and post-MI cardiac function were determined. BM from healthy donors, handled in the same manner, was used as a reference. Result: Of 26 cytokines analyzed, IL-6 showed a negative correlation with ECFC colony maximum in BM (estimate±SE (SEE) -0.13±0.04 P=0.007, multivariableR2: 0.59) and Healthy BM showed decreased ECFC colony outgrowth in the presence of IL-6 (P <0.05), in a dose-dependent manner. PDGF-BB positively correlated with CFU-EC colony maximum in BM (SEE 0.006± 0.002, P=0.023, R2: 0.22), MSC colony maximum in BM (SEE 0.006±0.002, P=0.023, R2: 0.17) and MSC colony maximum in PB (SSE 0.018±0.005, P=0.00005, R2:0.24). No significant correlations were found between cardiac function after AMI and PB cytokine levels. Conclusions: At 2-3 weeks after AMI, PB levels of the angiogenic cytokine, PDGF-BB and the pro-inflammatory cytokine, IL-6, were associated with BM cell phenotype and function. IL-6 has the potential to impair endothelial progenitor cell capacity; inhibiting IL-6 may be a target for improving the regenerative capacity of BM cells after AMI.

CXCR4+ CD45− Tissue-Committed Stem Cells (TCSC) for Myocardium Reside in the Bone Marrow, Are Mobilized into the Peripheral Blood during Myocardial Infarction, and “Home” to Infarcted Myocardium in CXCR4-SDF-1 and HGF/SF-c-Met Dependent Manner.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2131-2131
Author(s):  
Magda Kucia ◽  
Buddhadeb Dawn ◽  
Yiru Guo ◽  
Greg Hunt ◽  
Marcin Wysoczynski ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Peripheral Blood ◽  
Cardiac Differentiation ◽  
Specific Cell ◽  
Dependent Manner ◽  
Older Individuals ◽  
Hematopoietic Stem ◽  
Infarcted Myocardium

Abstract Several recent studies in animals as well as humans support the notion that bone marrow (BM)-derived cells participate in myocardial regeneration. However, this subject remains highly controversial and the identity of the specific cell type responsible for regeneration remains unknown. Recent work from our laboratory revealed that BM contains a highly mobile population of CXCR4+ cells that express mRNA for various markers of early tissue-committed stem cells (TCSC) and which are distinct from hematopoietic stem cells (HSC) (Leukemia2004:18;29–40). In the current study we investigated whether BM also contains a mobile pool of TCSC destined to differentiate into cardiomyocytes. Our data demonstrate that TCSC for cardiomyocytes (i) are present in significant amounts in BM harvested from young (1–2 month-old) while being barely detectable in older (1-year-old) mice; ii) reside in populations of murine BM-derived non-hematopoietic Sca-1+ CD45− cells and in population of human CXCR4+ CD34+ AC133+ CD45− BMMNC, iii) are mobilized from BM into peripheral blood (PB) during pharmacological mobilization or myocardial infarction; iv) the identified by us chemoattractants for these cells: stromal derived factor -1 (SDF-1), and hepatocyte growth factor/scatter factor (HGF/SF) are upregulated in infarcted myocardium, and v) blocking experiments with T140 (CXCR4 antagonist) and K252a (c-MET antagonist) confirmed that TCSC for cardiomyocytes are chemoattracted to the damaged myocardium in SDF-1-CXCR4 and SF/HGF-c-Met dependent manner. Thus, we conclude that the bone marrow is a potential source of TCSC for heart repair and since purified CD45+ HSC neither express cardiac markers nor differentiate in vitro into cardiomyocytes, we provide for the first time evidence that cardiac TCSC residing in bone marrow but not “plastic” HSC may account for cardiac differentiation of BM-derived cells. These observations provide rationale for further studies aimed at optimizing therapeutic cardiac regeneration by BM-derived non-hematopoietic cardiac TCSC. Finally, our observation that the number of marrow derived mobile/circulating cardiac TCSC is the highest in BM of young animals and decreases with age provides a novel insight into aging and may explain why the heart regeneration process becomes less effective in older individuals.

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&lt;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.

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