scholarly journals Intra-myocardial delivery of mesenchymal stem cells ameliorates left ventricular and cardiomyocyte contractile dysfunction following myocardial infarction

2010 ◽  
Vol 195 (2-3) ◽  
pp. 119-126 ◽  
Author(s):  
Qun Li ◽  
Subat Turdi ◽  
D. Paul Thomas ◽  
Tianjie Zhou ◽  
Jun Ren
2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  

AbstractBoth weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tong Wang ◽  
Zhi Wan ◽  
Wanchun Tang ◽  
Shijie Sun ◽  
Zitong Huang ◽  
...  

We investigated the effect of allogeneic mesenchymal stem cells (MSCs) on myoardial function following cardiopulmonary resuscitation (CPR) in a rat model of myocardial infarction. We further investigated the efficacy of three routes of MSCs administration including intravenous, intraventricular and intramyocardial injection. Regardless of administration routes, MSCs would improve myocardial function after CPR in myocardial infarction animals. Myocardial infarction was induced by ligation of the left anterior descending coronary artery in 54 rats (6 groups, 9 rats for each). One month later, animals were randomized to receive injection of 5×10 6 MSCs labeled with PKH26 or PBS alone as a placebo into right femoral vein or left ventricular cavity or the infarction zone in the anterior ventricular free wall. Four weeks after injection, 6 minutes of untreated ventricular fibrillation (VF) followed by 6 minutes of CPR were performed prior to defibrillation. Hemodynamics, including cardiac index (CI), dp/dt40, −dp/dt and left ventricular diastolic pressure(LVDP) were measured before induction of VF (baseline) and hourly following resuscitation. There were siginificant improvements in CI, dp/dt40(Figure 1 ), −dp/dt, LVDP after CPR in MSCs treated animals, regardless of the sites of injection. Survival time after CPR was siginificantly increased in MSCs trearted groups comparing with the corresponding PBS treated groups. Independent of administration routes, myocardial function and survival time after CPR were comparably improved in all groups treated with MSCs in constrast to the PBS groups. Figure 1


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiuyu Chen ◽  
Minjie Lu ◽  
Ning Ma ◽  
Gang Yin ◽  
Chen Cui ◽  
...  

Purpose.To track the fate of micron-sized particles of iron oxide (MPIO) labeled mesenchymal stem cells (MSCs) in vivo in a rat myocardial infarction model using 7T magnetic resonance imaging (MRI) scanner.Materials and Methods.Male MSCs (2 × 106/50 μL) dual-labeled with MPIO and CM-DiI were injected into the infarct periphery 7 days after myocardial infarction (MI). The control group received cell-free media injection. The temporal stem cell location, signal intensity, and cardiac function were dynamically assessed using a 7T MRI at 24 h before transplantation (baseline), 3 days, 2 weeks, and 4 weeks after transplantation, respectively.Results.MR hypointensities caused by MPIOs were observed on T2⁎-weighted images at all time points after MSCs injection. Cine-MRI showed that MSCs moderated progressive left ventricular remodeling. Double staining for iron and CD68 revealed that most of the iron-positive cells were CD68-positive macrophages. Real-time PCR for rat SRY gene showed the number of survival MSCs considerably decreased after transplantation. MSC-treated hearts had significantly increased capillary density in peri-infarct region and lower cardiomyocytes apoptosis and fibrosis formation.Conclusions.Iron particles are not a reliable marker for in vivo tracking the long-term fate of MSCs engraftment. Despite of poor cell retention, MSCs moderate left ventricular remodeling after MI.


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.


2019 ◽  
Vol 14 (12) ◽  
pp. 1077-1087
Author(s):  
Jun-Yan Xu ◽  
Hai-Yan Qian ◽  
Pei-Sen Huang ◽  
Jun Xu ◽  
Yu-Yan Xiong ◽  
...  

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement (‘fertilizing’) for cell-based therapy. Clinical Trial Registration: NCT03047772.


Sign in / Sign up

Export Citation Format

Share Document