Bench to Bedside
“Cardiac stem cell therapy involves delivering a variety of cells into hearts following myocardial infarction or chronic cardiomyopathy,” says Amit N. Patel, MD, MS, director of cardiac cell therapy at the University of Pittsburgh Medical Center and lead author of an overview and introductory article, Cardiac Stem Cell Therapy from Bench to Bedside. “Many questions remain, such as what types of cells may be most efficacious. Questions about dose, delivery method, and how to follow transplanted cells once they are in the body and questions about safety issues need answers. The following studies, contribute to the growing body of data that will move cell transplantation for heart patients closer to reality.”
According to Patel, special editor for this issue, suitable sources of cells for cardiac transplant will depend on the types of diseases to be treated. For acute myocardial infarction, a cell that reduces myocardial necrosis and augments vascular blood flow will be desirable. For heart failure, cells that replace or promote myogenesis, reverse apoptopic mechanisms and reactivate dormant cell processes will be useful.
“Very little data is available to guide cell dosing in clinical studies,” says Patel. “Pre-clinical data suggests that there is a dose-dependent improvement in function.”
Patel notes that the availability of autologous (patient self-donated) cells may fall short.
Determining optimal delivery methods raise issues not only of dose, but also of timing. Also, assessing the fate of injected cells is “critical to understanding mechanisms of action.”
Will cells home to the site of injury" Labeling stem cells with durable markers will be necessary and new tracking markers may need to be developed.
Improved cell survival drugs
Adult bone marrow-derived mensenchymal stem cells (MSCs) have shown great signaling and regenerative properties when delivered to heart tissues following a myocardial infarction (MI). However, the poor survival of grafted cells has been a concern of researchers. Given the poor vascular supply after a heart attack and an active inflammatory process, grafted cells survive with difficulty. Transmyocardial revasularization (TMR), a process by which channels are created in heart tissues by laser or other means, can enhance oxygenated blood supply.
“We hypothesized that using TMR as a scar pretreatment to cell therapy might improve the microenvironment to enhance cell retention and long-term graft success,” said Amit N. Patel, lead author of a study titled Improved Cell Survival in Infarcted Myocardium Using a Novel Combination Transmyocardial Laser and Cell Delivery System. “TMR may act synergistically with signaling factors to have a more potent effect on myocardial remodeling.”
Patel and colleagues, who used a novel delivery system to disperse cells in the TMR-generated channels in an animal model, report significant cell survival in the TMR+Cell group versus Cells or TMR alone. The researchers speculated that there was an increase in local production of growth factors that may have improved the survival of transplanted cells.Contact: Amit N. Patel, MD, MS, director of cardiac cell therapy, University of Pittsburgh Medical Center, McGowan Institute of Regenerative Medicine, 200 Lothrop Street – PUH C-700, Pittsburgh, PA 15213
“Our study suggests that the prolongation of SDF-1 expression at the time of an acute myocardial infarction (AMI) leads to the recruitment of what may be an endogenous stem cell in the heart,” says Marc Penn, MD, PhD, director of the Skirball Laboratory for Cardiovascular Cellular Therapeutics at the Cleveland Clinic Foundation. “These cells may contribute to increased contractile function even in their immature stage.”
In the study titled SDF-1 Recruits Cardiac Stem Cell Like Cells that Depolarize in Vivo, researchers concluded that there is a natural but inefficient stem cell-based repair process following an AMI that can be manipulated through the expression of key molecular pathways. The outcome of this inefficient repair can have a significant impact on the electrical and mechanical functions of the surviving myocardium.Contact: Marc Penn, MD, PhD, director, Skirball Laboratory for Cardiovascular Cellular Therapeutics, NE3, Departments of Cardiovascular Medicine and Cell Biology, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, Ohio, 44195.
“Our study demonstrated that bone marrow cell therapy associated with the surgical implantation onto the epicardium of a cell-seeded collagen type 1 matrix prevented myocardial wall thinning, limited post-ischemic remodeling and improved diastolic function,” says Juan Chachques, MD, PhD, lead author for Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Clinical Trial): One year follow-up.
“The use of the biomaterial appears to create a micro atmosphere where both exogenous and endogenous cells find an optimal microenvironment to repair tissues and maintain low scar production,” explains Chachques.
According to Chachques, the favorable effects may be attributed to several mechanisms. The BMC seeded in the collagen matrix may be incorporated into the myocardium through epicardial channels created at the injection sites. Too, the cell-seeded matrix may help prevent apoptosis.
“This biological approach is attractive because of its potential for aiding myocardial regeneration with a variety of cell types,” concluded Chachques.
Those cell types include skeletal myoblasts, bone marrow-derived mensenchymal stem cells, circulating blood-derived progenitor cells, endothelial and mesothelial cells, adipose tissue stem cells and, potentially, embryonic stem cells.Contact: Juan C. Chachques, MD, PhD, Department of Cardiovascular Surgery, Pompidou Hospital, 20 rue Leblanc, 75015 Paris, France.
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26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
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Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
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An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
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