Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction

2007 ◽  
Vol 293 (4) ◽  
pp. H2438-H2447 ◽  
Author(s):  
Robert W. Grauss ◽  
Elizabeth M. Winter ◽  
John van Tuyn ◽  
Daniël A. Pijnappels ◽  
Rebecca Vicente Steijn ◽  
...  

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immune-compromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 × 105cells in 20 μl, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/ scid mice. Sham-operated mice were used as the control ( n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 ± 2% vs. 36 ± 2%; P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 ± 3% vs. 16 ± 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 ± 0.3% of injected cells) expressed von Willebrand factor (16.9 ± 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning.

2010 ◽  
Vol 88 (4) ◽  
pp. 629-634 ◽  
Author(s):  
Cuiyu Bao ◽  
Jun Guo ◽  
Min Zheng ◽  
Yan Chen ◽  
Guosheng Lin ◽  
...  

Autologous or allogeneic mesenchymal stem cells (MSCs) have been used as one of the potential cell sources for cellular cardiomyoplasty. The adverse microenvironment in acute myocardial infarction, however, is considered a deleterious factor for MSC transplantation and cell survival. Tumor necrosis factor (TNF)-α is an inflammatory mediator produced during ischemia that may affect the survival of MSCs. In this study, we investigated the enhancement of MSC survival by transfecting cells with the TNF receptor (TNFR) gene, leading to the overproduction of TNFR and the binding of TNF-α. Rats with acute myocardial infarction, induced by the occlusion of the left coronary artery, were transplanted with MSC or MSC-TNFR. After 2 weeks of acute myocardial infarction, cardiac function was assessed. Engrafted MSC survival and localization of TNF-α protein in infarction myocardium were evaluated. The levels of TNF-α and TNFR in the infarction zone were assessed. The results indicate that MSC-TNFR transplantation (1) improved left ventricular function; (2) enhanced engrafted MSC survival in the infarcted myocardium; (3) attenuated the level of TNF-α in serum and cardiac tissue; and (4) increased TNFR protein production in the infarcted myocardium. Our results showed that MSC modified by the TNFR gene improved cell viability and thereby has the potential to improve the efficiency of MSC transplantation therapy in the ischemic heart.


2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Hadyanto Lim ◽  
Umar Zein ◽  
Ilham Hariaji

Background: Mesenchymal stem cells (MSCs) improve the cardiac function and remodeling in patients with ischemic heart disease. However, their presence in the circulating peripheral blood and post-transplantation has not been fully elucidated. We aimed to investigate the effects of intravenous transplantation of mobilized autologous peripheral blood on the number of MSCs in patients with ischemic heart disease. Methods: Granulocyte-colony stimulating factor (G-CSF, 5.0 μg/kg/day) was given subcutaneously once a day for five days to 7 patients (4 women and 3 men, aged 54-69 years) with ischemic heart disease. Leukapheresis procedure was started on the day 5 of G-CSF using the Spectra Optia cell separator. Circulating and intravenous transplantation of autologous MSCs after leukapheresis were analyzed by flow cytometry. MSCs were identified on the basis of dual positive cells (CD73 + /CD105 + or CD90 + /CD73 + or CD90 + /CD105 + ) and detected as MSCs if a cluster of at least 10 cells could be found. Results: MSCs in the circulating peripheral blood and after transplantation were detected in 2 (28%) and 6 (85%) patients, respectively. The frequency of intravenous peripheral blood MSCs increased significantly after transplantation (from 32.57 ± 22.76 x10 -4 % to 58.57 ± 28.49 x 10 -4 % , p<0.001). Moreover, there were significant rise in the total white blood cells count (from 10.25 ± 4.86 x 10 3 /μl to 35.81 ± 7.07 x 10 3 /μl, p<0.001) and the levels of CD34 + cells (from 1.17 ± 0.93 cells/μL to 138.30 ± 11.26 cells/μL, p<0.001) after the infusion. Conclusions: The results show that intravenous transplantation of mobilized autologous peripheral blood increases the number of MSCs in patients with ischemic heart disease. Leukapheresis product of peripheral blood MSCs could therefore be a potential source for autologous transplantation in ischemic heart disease.


2013 ◽  
Vol 3 (2) ◽  
pp. 50-56
Author(s):  
MBK Choudhury ◽  
MM Hossain ◽  
M Akhtaruzzaman ◽  
MM Jamal Uddin ◽  
MS Rahman ◽  
...  

Magnesium (Mg) and potassium (K) are the major intracellular cations whose presence in the serum are low, but minor changes of those may show a remarkable change in the various body functions specially in the heart. The study was designed to find out the correlation between serum Mg and K in acute myocardial infarction (AMI), chronic ischemic heart disease (CIHD) and normal healthy volunteers. It was carried out over a period of 18 months in the Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University (BSMMU) in collaboration with Department of Cardiology, Sir Salimullah Medical College & Mitford Hospital (SSMC & MH) and Atomic Energy Center, Dhaka. A total of 101 subjects were included in which 32 subjects were AMI, 34 CIHD and 35 normal healthy volunteers. Serum glucose and serum creatinine were estimated to exclude diabetes and renal dystrophies. Estimation of serum CK-MB and ECG tracing were done as diagnostic tools of AMI and to categories the subjects into various groups. Serum Mg was estimated by Atomic absorption spectrophotometer and serum K by Ion sensitive electrode. The present study shows that there is a strong positive correlation of serum Mg and K in AMI, CIHD and healthy control subjects (r = 0.566, p<0.01 level). So it is suggested to estimate and supplement both Mg and K in IHD patients for their better management. DOI: http://dx.doi.org/10.3329/bjmb.v3i2.13812 Bangladesh J Med Biochem 2010; 3(2): 50-56


2020 ◽  
Author(s):  
Kamal Khademvatani ◽  
Amin Sedokani ◽  
Sima Masudi ◽  
Parisa Nejati ◽  
Mir Hossein Seyed-Mohammadzad ◽  
...  

AbstractAimMyocardial infarction (MI) is one of the most important cardiovascular diseases. A trigger is an external stimulus, potential to create a pathological change leading to a clinical event. In addition to classic risk factors of ischemic heart disease and myocardial infarction, MI triggers play critical roles in the incidence of acute MI.Methods and ResultsThis is a cross-sectional study of 254 patients with the first acute myocardial infarction referring to Seyedoshohada heart center of Urmia, Iran were enrolled in the study within one year of study. After 48h of hospitalization and, treatment, and cardiac caring, the patients were provided with the questionnaire to collecting the history of the disease ad triggers. In addition to laboratory and paraclinical data, the analysis of the study was performed. Out of 220 (86.4%) patients with STEMI and 34 (13.6%) patients with NSTEMI, there were significant differences (P-value <0.05) in AMI triggers with LVEF (0.03), gender (0.027), residency and living area (0.039), occupation (0.002), smoking (0.008), abnormal serum TG levels (0.018) and the season of AMI occurrence (0.013). The mean age for AMI patients was 60.4±12.97 years old with a mean BMI of 26.65±4.35 kg/m2.ConclusionIn addition to classic risk factors of ischemic heart disease and myocardial infarction, health care systems and physicians must pay more attention to triggers that may induce an acute myocardial infarction in people with predisposing factors especially in the male sex, stressful and hand working jobs, and psychological and mental tension patients.


Circulation ◽  
2020 ◽  
Vol 142 (18) ◽  
pp. 1725-1735
Author(s):  
Renato D. Lopes ◽  
Karen P. Alexander ◽  
Susanna R. Stevens ◽  
Harmony R. Reynolds ◽  
Gregg W. Stone ◽  
...  

Background: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction is ≥35% but <45% is unknown. Methods: Among 5179 participants randomized into ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD. Median follow-up was 3.2 years. Results: There were 398 (7.7%) participants with HF/LVD at baseline, of whom 177 had HF/LVEF >45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. HF/LVD was associated with more comorbidities at baseline, particularly previous myocardial infarction, stroke, and hypertension. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (4-year cumulative incidence rate, 22.7% versus 13.8%; cardiovascular death or myocardial infarction, 19.7% versus 12.3%; and all-cause death or HF, 15.0% versus 6.9%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% versus 29.3%; difference in 4-year event rate, −12.1% [95% CI, −22.6 to −1.6%]), whereas those without HF/LVD did not (13.0% versus 14.6%; difference in 4-year event rate, −1.6% [95% CI, −3.8% to 0.7%]; P interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and cardiovascular mortality when invasive versus conservative strategy–associated outcomes were analyzed with LVEF as a continuous variable for patients with and without previous HF. Conclusions: ISCHEMIA participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%, an initial invasive approach was associated with better event-free survival. This result should be considered hypothesis-generating. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01471522.


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