Mayo Clinic investigators, with Belgian collaborators, have demonstrated that rationally "guided" human adult stem cells can effectively heal, repair and regenerate damaged heart tissue. The findings -- called "landmark work" in an accompanying editorial -- appear in today's Journal of the American College of Cardiology.
Stem cells isolated from patients have normally a limited capacity to repair the heart. This innovative technology boosts the regenerative benefit by programming adult stem cells to acquire a cardiac-like profile. Primed by a cocktail of recombinant cardiogenic growth factors, mesenchymal stem cells (MSCs) harvested from the bone marrow of a cohort of patients with coronary artery disease showed "superior functional and structural benefit without adverse side effects" over a 1-year follow-up in a model of heart failure according to the study.
Significance of the Findings
"These findings provide proof-of-principle that "smart" adult stem cells have added benefit in repairing the heart, providing the foundation for further clinical evaluation," says Andre Terzic, M.D., Ph.D., Mayo Clinic researcher and senior investigator of the study. "The successful use of guided "lineage specified" human stem cells is based on natural cardiogenic cues" adds Atta Behfar, M.D., Ph.D. first author of the study. The pre-clinical data reported in this seminal paper have cleared the way for safety and feasibility trials in humans, which were recently conducted in Europe.
In their editorial, Eduardo Marban, M.D., Ph.D., and Konstantinos Malliaras, M.D., of Cedars-Sinai Heart Institute, in Los Angeles describe the Mayo approach as a "boot camp" for stem cells and also write that the study "… provides the first convincing evidence that MSCs, at least in vitro, can in fact become functional cardiomyocytes (heart cells) …"
The long-term potential of the findings include development of an effective regenerative medicine therapy for patients with chronic heart failure.
How It Was Done
Researchers obtained bone marrow-derived stem cells from heart disease patients undergoing coronary bypass surgery. Testing of these stem cells revealed that cells from two of 11 individuals showed an unusual capacity for heart repair. These rare cells demonstrated upregulated genetic transcription factors that helped identify a molecular signature identifying highly regenerative stem cells. The cardiogenic cocktail was then used to induce this signature in non-reparative patient stem cells to program their capacity to repair the heart. Mouse models with heart failure, injected with these cells, demonstrated significant heart function recovery along with improved survival rate after a year, compared to those treated with unguided stem cells or saline.
Specifically, researchers found that the heart tissue healed more effectively; that human cardiac and vascular cells were found participating in the regeneration, repair and strengthening of heart structures within the area of injury; and that scars and vestiges of heart damage appeared to fade away.
Authors include Atta Behfar, M.D., Ph.D.; Satsuki Yamada, M.D., Ph.D.; Ruben Crespo-Diaz; Jonathan Nesbitt; Lois Rowe; Carmen Perez-Terzic, M.D., Ph.D.; Andre Terzic, M.D., Ph.D. of Mayo Clinic; Vinciane Gaussin, Ph.D. and Christian Homsy, M.D., Cardio3 Biosciences, Mont-Saint-Guibert, Belgium; and Jozef Bartunek, M.D., Cardiovascular Center, Aalst, Belgium.
The research was supported by the National Institutes of Health, the American Heart Association, the Marriott Heart Disease Research Program, Cardio 3 Biosciences, the Ted Nash Long Life Foundation, the Ralph Wilson Medical Research Foundation, the Mayo Clinic General Mills Clinician-Investigator Fellowship, and Mayo Clinic.
Mayo Clinic and Drs. Andre Terzic and Atta Behfar have a financial interest associated with technology related to this research program. In accordance with the Bayh-Dole Act, Mayo Clinic has licensed that technology to Cardio 3 Biosciences in exchange for equity. No royalties have accrued to date to the institution or the inventors.
About Mayo Clinic
For more than 100 years, millions of people from all walks of life have found answers at Mayo Clinic. These patients tell us they leave Mayo Clinic with peace of mind knowing they received care from the world's leading experts. Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. At Mayo Clinic, a team of specialists is assembled to take the time to listen, understand and care for patients' health issues and concerns. These teams draw from more than 3,700 physicians and scientists and 50,100 allied staff that work at Mayo Clinic's campuses in Minnesota, Florida, and Arizona; and community-based providers in more than 70 locations in southern Minnesota, western Wisconsin and northeast Iowa. These locations treat more than half a million people each year. To best serve patients, Mayo Clinic works with many insurance companies, does not require a physician referral in most cases and is an in-network provider for millions of people. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education visit www.mayo.edu. MayoClinic.com (www.mayoclinic.com) is available as a resource for your general health information.
Robert Nellis | EurekAlert!
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
Pollen taxi for bacteria
18.07.2018 | Technische Universität München
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
18.07.2018 | Life Sciences
18.07.2018 | Materials Sciences
18.07.2018 | Health and Medicine