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.
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
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23.02.2018 | Physics and Astronomy