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!
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy