The study, published in Nature Biotechnology, also shows that there was an effect on driving the formation of a small number of new cardiac muscle cells.
"This is the beginning of using the heart as a factory to produce growth factors for specific families of cardiovascular stem cells, and suggests that it may be possible to generate new heart parts without delivering any new cells to the heart itself ", says Kenneth Chien, a Professor at the medical university Karolinska Institutet in Sweden and Harvard University, US, who led the research team behind the new findings.
The study is based upon another recent discovery in the Chien lab, which was published in Cell Research. This study shows that VEGFA, a known growth factor for vascular endothelial cells in the adult heart, can also serve as a switch that converts heart stem cells away from becoming cardiac muscle and towards the formation of the coronary vessels in the fetal heart. To coax the heart to make the VEGFA, the investigators in the Nature Biotechnology study used new technology where synthetic messenger RNA (mRNA) that encodes VEGFA is injected into the muscle cell. Then, heart muscle produces a short pulse of VEGFA. The mRNA is synthetically modified so that it escapes the normal defense system of the body that is known to reject and degrade the non-modified mRNA as a viral invader.
The study, performed in mice, shows that only a single administration of a short pulse of expression of VEGFA is required, if it can be delivered to the exact region where the heart progenitors reside. The therapeutic effect is long term, as shown by markedly improved survival following myocardial infarction with a single administration of the synthetic mRNA when given within 48 hours after the heart attack. The long-term effect appears to be based on changing the fate of the native heart stem cells from contributing to cardiac fibrotic scar tissue and towards cardiovascular tissue.
"This moves us very close to clinical studies to regenerate cardiovascular tissue with a single chemical agent without the need for injecting any additional cells into the heart." says Professor Chien.
At the same time, he points out that these are still early days and there remains much to be done. In particular, it will become of interest to engineer new device technology to deliver the synthetic mRNA via conventional catheter technology. It also will be critical to move these studies, which are based in mouse models, to other animals, which is currently in progress.
The platform technology is being developed for clinical use by the company Moderna Therapeutics, which was co-founded by Kenneth Chien. A recently announced collaboration with AstraZeneca will support moving the synthetic modified mRNA therapeutics for regenerative cardiology into the clinical setting. This work was also funded with grants from the US National Institutes of Health and The Croucher Foundation, amongst others.
Publication: 'Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction', Lior Zangi, Kathy O Lui, Alexander von Gise, Qing Ma, Wataru Ebina, Leon M Ptaszek, Daniela Später, Huansheng Xu, Mohammadsharif Tabebordbar, Rostic Gorbatov, Brena Sena, Matthias Nahrendorf, David M Briscoe, Ronald A Li, Amy J Wagers, Derrick J Rossi, William T Pu & Kenneth R Chien, Nature Biotechnology, online 8 September 2013, DOI: 10.1038/nbt.2682.
Journal website: http://www.nature.com/nbt
To download images and contact the Press Office: ki.se/pressroom
Karolinska Institutet -- a medical university: ki.se/english
Katarina Sternudd | EurekAlert!
Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel
Oxygen loss in the coastal Baltic Sea is “unprecedentedly severe”
05.07.2018 | European Geosciences Union
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Earth Sciences
19.07.2018 | Power and Electrical Engineering
19.07.2018 | Materials Sciences