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!
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy