Stem Cells In Myocardial Infarction Research Articles

Stem cells for myocardial infarction

Stem cells for myocardial infarction

Cell therapy: Promise fulfilled?

Cellular immunotherapy has been widely accepted as a new powerful modality of cancer treatment. The last 2 decades have seen impressive results in its application against haemato-oncologic malignancies, melanomas and prostate carcinoma. Cellular immunotherapy has since found applicability beyond cancer into autoimmunity and continues to expand in its clinical applicability. The discovery that stem cells have the ability to differentiate into more mature cell types, like neurones and myocardium, has focused research on using exogenous cells to repair damaged tissues. This led to numerous clinical trials using stem cells in myocardial infarction, cardiomyopathy and spinal cord damage. Results have ranged from modest to significant clinical outcomes with continuing debate on the exact process of regeneration achieved. The intertwining between cell therapy and transfusion medicine now includes research on progenitor cells for the production of mature red cells. It is also clear that cell therapy has enabled an improved understanding of the pathogenesis and clinical course of many diseases, while perhaps its role in regenerative medicine is most enticing. However, the critical role of manufacturing in terms of cost, complexity, reproducibility, and regulatory matters remains a central issue in the consideration of whether cell therapy has met all of its promise.

EXPERIENCE AND PROSPECTS OF THE CLINICAL APPLICATION OF MESENCHYMAL STEM CELLS

Tandem transplantation of hemopoeitic and mesenchymal stem cells is a perspective and now widely used direction of cell therapy of oncohematological diseases and multiple sclerosis in the clinical practice of the Republic of Belarus. Mesenchymal stem cells are also effectively used as concomitant immunosuppressive therapy of acute and chronic reaction Transplant Against Host (RTAH). The protocols of the application of mesenchymal stem cells for the therapy of oncohematological patients and patients with multiple sclerosis are approved by the Ministry of Public Health Care of the Republic of Belarus. The efficacy of the cell therapy with the use of mesenchymal stem cells is studied in the clinical research in the treatment for various diseases: genetic degenerative diseases of skeleton, ischemic disease, liver cirrhosis, neurodegenerative diseases (parkinsonism, Alzheimer's disease). The experimental work and clinical trials have shown the positive effect of the transplantation of mesenchymal stem cells in myocardial infarction and in the substitutive therapy of liver impairment.

Adipose-derived Stem Cells for Myocardial Infarction

In recent years, stem cell treatment of myocardial infarction has elicited great enthusiasm upon scientists and physicians alike, thus making the finding of a suitable cell a compulsory subject for modern medicine. Due to its potential, accessibility and efficiency of harvesting, adipose tissue has become one of the most attractive sources of stem cells for regenerative therapies. The differentiation capacity and the paracrine activity of these cells has made them an optimal candidate for the treatment of a diverse range of diseases from immunological disorders as graft versus host disease to cardiovascular pathologies like peripheral ischemia. In this review, we will focus on the use of stem cells derived from adipose tissue for treatment of myocardial infarction, with special attention to their putative in vivo mechanisms of action.

Stem cells in myocardial infarction: from bench to bedside

Acute myocardial infarction (AMI) often leads to congestive heart failure, a condition associated with high subsequent mortality. Pharmacological treatment and, more importantly, primary angioplasty have notably decreased early mortality and...

Instent neointimal hyperplasia after percutaneous intervention for ST-elevation myocardial infarction and treatment with granulocyte-colony stimulating factor. Results from the stem cells in myocardial infarction (STEMMI) trial

BackgroundRecombinant granulocyte-colony stimulating factor (G-CSF) mobilized pluripotent cells from the bone marrow are proposed to have a regenerative potential. Though, a report of excessive instent restenosis, in patients treated with G-CSF before percutaneous coronary intervention (PCI) warrants caution. MethodsPatients (n=59) enrolled in the STEMMI trial, a randomized and double blind study, comparing G-CSF and placebo after large ST-elevation myocardial infarctions, had an intracoronary ultrasound imaging at 6 months follow-up with a quantitative analysis of instent neointimal hyperplasia. ResultsDuring G-CSF treatment leukocyte counts, and CD34+ and CD45−/CD34− cell fractions in peripheral blood increased markedly (p<0.0001 vs. placebo). At follow-up, there were no differences in intracoronary late lumen loss, expressed as neointima volume per mm of stent (1.6 mm3±1.2 [G-CSF group] vs. 1.9 mm3±1.3 [placebo group]; p=0.38), and in minimal instent lumen area (5.4 mm2±2.4 vs. 5.3 mm2±2.6, p=0.90). In the placebo group, plasma concentration of stromal cell-derived factor-1 (SDF-1) increased significantly after STEMI. This SDF-1 response was completely suppressed during G-CSF treatment. A rebound increase of SDF-1 was observed after withdrawal of G-CSF (p=0.001). Plasma concentration of SDF-1 at the time of stent implantation correlated positively to neointimal hyperplasia (p=0.025). ConclusionsG-CSF treatment, initiated after PCI, does not lead to excessive instent neointimal hyperplasia or restenosis in patients with STEMI. The timing of G-CSF, in relation to the PCI, might be important, as G-CSF influences SDF-1.

MR imaging of injected magnetically labeled stem cells in myocardial infarction: experiment with pigs

To investigate the efficacy of magnetic resonance imaging (MRI) in tracking bone marrow derived mononuclear cells (BM-MNCs) labeled with superparamagnetic iron oxide (SPIO) nanoparticles. BM-MNCs were isolated from the bone marrow of 14 pigs. These 14 pigs underwent occlusion of the left anterior descending coronary artery (LAD) to establish myocardial infarction (MI) models and then randomly divided into 2 groups: experimental group (n = 9) to be injected with BM-MNCs labeled with SPIO intracoronarily under X-ray fluoroscopy, and control group (n = 5), to be injected with unlabelled BM-MNCs MRI was performed with a 1.5T MR scanner to demonstrate the location of the BM-MNCs once a week. T pigs were killed when no labeled BM-MSC was detected. The hearts were taken out to undergo HE staging and Prussian blue staining. Immunohistochemistry was used to detect the desmin and myosin. The cell labeling efficiency was almost 100%. Contrast-enhanced MRI demonstrated successful establishment of MI models. Effective MRI tracking findings were obtained in 8 pigs, 7 of the experimental group and 3 of the control group. In 3 pigs T2* weighted MRI showed the zone of labeled cell accumulation shows vague low-signal area around the infarction area and much better conspicuity of the zone of hypoenhancement was shown under contrast-enhanced MRI. The hypoenhancement zone disappeared 14 - 21 days after the injection of BM-MSCs. Histological analyses showed that most Prussian blue positive cells were well correlated with the area where a signal intensity loss was observed in MRI. 1.5T MR imaging can monitor the magnetically labeled BM-MNC in vivo in myocardial infarction provided the number of injected is nor less than 10(6).

Stem Cell Mobilization Induced by Subcutaneous Granulocyte-Colony Stimulating Factor to Improve Cardiac Regeneration After Acute ST-Elevation Myocardial Infarction: Result of the Double-Blind, Randomized, Placebo-Controlled Stem Cells in Myocardial Infarction (STEMMI) Trial

Stem Cell Mobilization Induced by Subcutaneous Granulocyte-Colony Stimulating Factor to Improve Cardiac Regeneration After Acute ST-Elevation Myocardial Infarction: Result of the Double-Blind, Randomized, Placebo-Controlled Stem Cells in Myocardial Infarction (STEMMI) Trial

Cardiac Stem Cell Therapy

Cardiovascular disease remains the number one cause of morbidity and mortality in the United States and Europe. In the United States alone, ≈1 million patients suffer a myocardial infarction every year, with an associated mortality of 25% at 3 years.1 A more sobering statistic is the fact that there are ≈5 million Americans with congestive heart failure, with an associated 20% mortality per year. This remains the case despite advances in pharmacotherapy, cardiac resynchronization therapies, and the use of implantable cardioverter-defibrillators.2 Some patients with end-stage congestive heart failure are considered for cardiac transplantation, but the demand for this therapeutic approach greatly outweighs the availability of donor hearts. Over the past few years, several animal studies and a few clinical trials have supported the use of stem cells as a potential therapeutic modality to address this unmet clinical need. Response by Boyle et al p 358 Several different types of cells have been used in both animal studies and patients to promote the repair of damaged myocardium. The 2 main sources of stem cells are adult stem and embryonic stem (ES) cells. ### ES Cells ES cells are derived from the inner mass of developing embryos during the blastocyst stage. Characteristic features of ES cells include their proliferative and self-renewing properties and their ability to differentiate into a wide variety of cell types, including cardiac myocytes.3 The major concerns with their use in human trials include the formation of teratomas when ES cells are injected into immunocompromised animals. This is particularly important because the ES cells currently available for use in humans would be of allogeneic origin and therefore would require immunosuppression. As nuclear transfer techniques improve, they will provide a way of generating an unlimited supply of histocompatible ES cells using the nuclei of cells obtained directly from the recipient …

Issue Highlights

HomeCirculationVol. 113, No. 16Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published25 Apr 2006https://doi.org/10.1161/circ.113.16.1921Circulation. 2006;113:1921NON–TRANSFERRIN-BOUND IRON AND RISK OF CORONARY HEART DISEASE IN POSTMENOPAUSAL WOMEN, by van der A et al.The parallel rise in both body iron stores and vascular risk in women after menopause led to the ‘iron overload‘ theory of coronary heart disease (CHD). Epidemiological studies relating serum ferritin levels to CHD risk have yielded inconsistent results, however. In this issue of Circulation, van der A and colleagues evaluated a community-based sample of postmenopausal women to test the hypothesis that a labile iron component associated with non--transferrin-bound iron (NTBI) might be more suitable for relating to CHD risk. The investigators noted that women in the highest NTBI tertile had a statistically significant 53% lower risk of acute myocardial infarction and a nonsignificant 16% lower risk of CHD compared with those in the lowest tertile in multivariable analyses. Similar results were obtained for serum iron, transferrin saturation, and serum ferritin. These observations do not support the presence of an excess risk of CHD or myocardial infarction in postmenopausal women with relatively higher levels of NTBI or other measures of iron overload. See p 1942.STEM CELL MOBILIZATION INDUCED BY SUBCUTANEOUS GRANULOCYTE-COLONY STIMULATING FACTOR TO IMPROVE CARDIAC REGENERATION AFTER ACUTE ST-ELEVATION MYOCARDIAL INFARCTION: RESULT OF THE DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STEM CELLS IN MYOCARDIAL INFACTION (STEMMI) TRIAL, by Ripa et al.Percutaneous coronary revascularization procedures restore coronary flow quickly in patients with acute ST-elevation myocardial infarction, and yet there is often some degree of myocardial necrosis resulting in left ventricular dysfunction. To prevent adverse ventricular remodeling, efforts have been devoted to determining the therapeutic efficacy of bone-marrow–derived stem cells in preserving ventricular function. These cells have been isolated ex vivo and infused into the coronary artery or have been stimulated to exit the bone marrow to home to sites of myocardial injury by the administration of granulocyte-colony stimulating factor (G-CSF). Early open-label studies have demonstrated the safety and potential efficacy of G-CSF. In this issue of Circulation, Ripa et al present data from the STEM cells in Myocardial Infarction (STEMMI) Trial. This is the first report of a randomized, double-blind, placebo-controlled trial of G-CSF in patients with ST-elevation myocardial infarction and successful percutaneous revascularization. See p 1983.MACROPHAGE METALLOELASTASE ACCELERATES THE PROGRESSION OF ATHEROSCLEROSIS IN TRANSGENIC RABBITS, by Liang et al.In this issue of Circulation, Liang et al used a novel approach involving the generation of transgenic rabbits to study the role of the macrophage metalloelastase (matrix metalloproteinase [MMP]-12) in atherosclerosis. Their results indicate that MMP-12 causes media destruction and pseudoaneurysm formation and accelerates plaque growth in an animal model that more closely resembles atherosclerosis in humans. This transgenic rabbit model may offer new insights into the roles of MMPs in extracellular matrix remodelling and cellular migration in atherosclerotic lesion formation that may challenge some prior conclusions based on mouse models. See p 1993.Visit http://circ.ahajournals.org:Cardiology Patient PageSyncope. See p e715.Images in Cardiovascular MedicineNatural Tissue Engineering Inside a Ventricular Septum Defect Occluder. See p e718. Download figureDownload PowerPointTransition From Left Ventricular Hypertrophy to Massive Fibrosis in the Cardiac Variant of Fabry Disease. See p e720.External Carotid Artery--Internal Jugular Vein Fistula: A Complication of Internal Jugular Cannulation. See p e722.CorrespondenceSee p e724. Previous Back to top Next FiguresReferencesRelatedDetails April 25, 2006Vol 113, Issue 16 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.113.16.1921 Originally publishedApril 25, 2006 PDF download Advertisement

Stem cells for myocardial infarction: we're not there yet

Stem cells for myocardial infarction: we're not there yet

In Vivo Magnetic Resonance Imaging of Mesenchymal Stem Cells in Myocardial Infarction

We investigated the potential of magnetic resonance imaging (MRI) to track magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. Adult farm pigs (n=5) were subjected to closed-chest experimental MI. MR-MSCs (2.8 to 16x107 cells) were injected intramyocardially under x-ray fluoroscopy. MRIs were obtained on a 1.5T MR scanner to demonstrate the location of the MR-MSCs and were correlated with histology. Contrast-enhanced MRI demonstrated successful injection in the infarct and serial MSC tracking was demonstrated in two animals. MRI tracking of MSCs is feasible and represents a preferred method for studying the engraftment of MSCs in MI.