Effects of intracoronary delivery of allogenic bone marrow-derived stem cells expressing heme oxygenase-1 on myocardial reperfusion injury

2012 ◽  
Vol 108 (09) ◽  
pp. 464-475 ◽  
Author(s):  
Michal Tendera ◽  
Wieslaw Cybulski ◽  
Ewa K. Zuba-Surma ◽  
Krzysztof Szade ◽  
Urszula Florczyk ◽  
...  

SummaryHeme oxygenase-1 (HO-1) decreases apoptosis, inflammation and oxidative stress. The aim of the study was to investigate the effects of intracoronary infusion of allogenic bone marrow cells (BMC) overexpressing HO-1 in the porcine model of myocardial infarction (MI). MI was produced by balloon occlusion of a coronary artery. BMC were transduced with adenoviruses encoding for HO-1 (HO-1 BMC) or GFP (GFP-BMC) genes. Prior to reperfusion animals received HO-1 BMC, control BMC (unmodified or GFP-BMC) or placebo. Left ventricular (LV) ejection fraction (EF), shortening fraction (SF), end-systolic and enddiastolic diameters (EDD, ESD) were assessed by echocardiography before, 30 minutes (min) and 14 days after reperfusion. BMC significantly improved LVEF and SF early (30 min) after reperfusion as well as after 14 days. Early after reperfusion HO-1 BMC were significantly more effective than control BMC, but after 14 days, there were no differences. There were no effect of cells on LV remodelling and diastolic function. Both HO-1 BMC and control BMC significantly reduced the infarct size vs. placebo (17.2 ± 2.7 and 18.8 ± 2.5, respectively, vs. 27.5 ± 5.1, p= 0.02) in histomorphometry. HO-1-positive donor BMC were detected in the infarct border area in pigs receiving HO-1-cells. No significant differences in expression of inflammatory genes (SDF-1, TNF-α, IL-6, miR21, miR29a and miR133a) in the myocardium were found. In conclusion, intracoronary delivery of allogeneic BMC immediately prior to reperfusion improved the LVEF and reduced the infarct size. HO-1 BMC were not superior to control cells after 14 days, however, produced faster recovery of LVEF. Transplanted cells survived in the peri-infarct zone.

Blood ◽  
1963 ◽  
Vol 22 (1) ◽  
pp. 44-52 ◽  
Author(s):  
GEORGES MATHÉ ◽  
JEAN-LOUIS AMIEL ◽  
LÉON SCHWARZENBERG ◽  
ANNE-MARIE MERY ◽  
F. Lapeyraque

Abstract Preservation of a graft of lymph node cells or semi-allogenic bone marrow cells at 37 C. in Tyrode’s solution for 2 hours, which reduces the percentage of cells not permeable to eosin by half, has a statistically significant reducing effect on the frequency of acute or chronic secondary syndromes which occur in irradiated recipients. Preservation at 18 C. for 6 hours, which in the same way increases the percentage of cells permeable to eosin, does not have the same effect. These two methods of preserving bone marrow cells do not appreciably reduce the myeloid-restoring capacity of compatible or incompatible irradiated recipients. Application of these results to bone marrow grafting in clinical medicine is discussed.


2016 ◽  
Author(s):  
O. V. Kokorev ◽  
V. N. Hodorenko ◽  
N. V. Cherdyntseva ◽  
V. E. Gunther

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Rebecca E Tee

Background: Reperfusion injury occurring after reestablishment of blood flow after MI is thought to be mediated by reactive oxygen species and neutrophilic cellular damage. The Heme-Oxygenase-1 (HO-1) dependent decrease in oxidative stress may attenuate injury in part by inhibiting transcription factor NFκB-mediated inflammation. We tested the hypothesis that exogenous upregulation of HO-1 by hemin administration confers acute and chronic cardioprotection against I/R injury in rats and attenuates LV remodeling post-infarction. Methods: Six week-old male Wistar rats were randomly assigned to sham, vehicle, or hemin-treated groups. Vehicle and hemin were administered i.p. once daily for 3 days prior to LAD occlusion, and 48 hours post-operatively once every 3 days. Infarct size was determined by H&E histological analysis and fibrosis was quantified by Masson’s Trichrome staining. We used transthoracic echocardiography to assess LV size, function and wall motion. Results: Hemin increased HO-1 expression and decreased infarct size and fibrosis, and attenuated LV wall thinning and chamber dilatation in the short-term (4 days post-infarction). The decrease in infarct size and fibrosis in the hemin group was accompanied by a decrease in NF-κB activity. We observed no significant difference in infarct size and area of fibrosis between hemin and vehicle-treated groups at 3 months (p=0.6681, p=0.6382, respectively). Cavity dilatation did not differ between the two groups at 3 months, however attenuated interventricular septum thinning (p<0.05) was observed in the hemin group compared with the vehicle group. Conclusion: HO-1 upregulation by hemin confers acute cardioprotection and decreased inflammation, possibly by inhibiting NF-κB activity, although chronic treatment with hemin does not prevent long-term LV remodeling post-MI. Future research should focus on optimal HO-1 upregulation to attenuate long-term LV remodeling due to reperfusion injury. Left Ventricle Wall and Chamber Dimensions


Heart ◽  
2021 ◽  
pp. heartjnl-2021-319359
Author(s):  
Tejas Deshmukh ◽  
Peter Emerson ◽  
Paul Geenty ◽  
Shehane Mahendran ◽  
Luke Stefani ◽  
...  

ObjectiveTo evaluate the utility of two-dimensional multiplanar speckle tracking strain to assess for cardiotoxicity post allogenic bone marrow transplantation (BMT) for haematological conditions.MethodsCross-sectional study of 120 consecutive patients post-BMT (80 pretreated with anthracyclines (BMT+AC), 40 BMT alone) recruited from a late effects haematology clinic, compared with 80 healthy controls, as part of a long-term cardiotoxicity surveillance study (mean duration from BMT to transthoracic echocardiogram 6±6 years). Left ventricular global longitudinal strain (LV GLS), global circumferential strain (LV GCS) and right ventricular free wall strain (RV FWS) were compared with traditionl parameters of function including LV ejection fraction (LVEF) and RV fractional area change.ResultsLV GLS (−17.7±3.0% vs −20.2±1.9%), LV GCS (−14.7±3.5% vs −20.4±2.1%) and RV FWS (−22.6±4.7% vs −28.0±3.8%) were all significantly (p=0.001) reduced in BMT+AC versus controls, while only LV GCS (−15.9±3.5% vs −20.4±2.1%) and RV FWS (−23.9±3.5% vs −28.0±3.8%) were significantly (p=0.001) reduced in BMT group versus controls. Even in patients with LVEF >53%, ~75% of patients in both BMT groups demonstrated a reduction in GCS.ConclusionMultiplanar strain identifies a greater number of BMT patients with subclinical LV dysfunction rather than by GLS alone, and should be evaluated as part of post-BMT patient surveillence. Reduction in GCS is possibly due to effects of preconditioning, and is not fully explained by AC exposure.


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