Many people who survive a heart attack find themselves back in the hospital with a failing heart just years later. And the outcome often is unfavorable, owing to limited treatment options.
But scientists at Temple University School of Medicine's Cardiovascular Research Center (CVRC) recently found hope in an unlikely source – stem cells in cortical, or compact, bone. In a new study, they show that when it comes to the regeneration of heart tissue, these novel bone-derived cells do a better job than the heart's own stem cells.
According to the study's senior investigator, Steven R. Houser, Ph.D., FAHA, Chairperson of Temple's Department of Physiology and Director of the CVRC, it is early days for cortical bone-derived stem cells (CBSCs). Nonetheless, his team's findings, featured on the cover of the August 16th issue of Circulation Research, have considerable implications for stem cell therapy for the heart.
A major challenge in the treatment of heart attack is early intervention, which is key to reducing the chances for long-term complications, such as heart failure. When it comes to stem cells, Houser said, "The strategy is to inject the cells right after [a heart attack]." Currently, though, that approach works only in animal studies. To make it work in humans, Houser explained, "we need cells right off the rack and ready to go clinically."
CBSCs could be those cells. Stem cells are youthful by degrees, and CBSCs are considered some of the most pluripotent – like human newborns, naïve and ready to become anything. But while CBSCs and similarly pluripotent stem cells retain the ability to develop into any cell type needed by the body and sometimes bring their youthful energy to the aid of mature cells – making them especially appealing for therapeutics – they also have the potential to wander off course, possibly landing themselves in unintended tissues. Cardiac stem cells, on the other hand, are a little more capable and a little more set in their ways, like toddlers. While they may need some coaxing into action, they are more likely to stay in their resident tissue.
To figure out how CBSCs might behave in the heart in the first place, Houser's team, led by Temple graduate student Jason Duran, began by collecting the cells from mouse tibias. The particular mice used had been engineered with green fluorescent protein (GFP), which meant that the CBSCs carried a green marker to allow for their later identification. The cells were then expanded in petri dishes in the laboratory before being injected directly into the hearts of non-GFP mice that had suffered heart attacks. Some mice received cardiac stem cells instead of CBSCs.
In the following weeks, as the team monitored the progress of the mice, they found that the youthfulness of the CBSCs had prevailed. The cells had triggered the growth of new blood vessels in the injured tissue, and six weeks after injection, they had differentiated, or matured, into heart muscle cells. While generally smaller than native heart cells, the new cells had the same functional capabilities, and overall they had improved survival and heart function. Similar improvements were not observed in the subset of mice treated with cardiac stem cells. Nor was there evidence in those mice that the cardiac cells had undergone differentiation.
The findings challenge the general assumption that cardiac stem cells, because they reside in the heart, are the cells most capable of repairing damaged heart tissue. For that reason, according to Houser, the new paper likely will be controversial.
"What we did generates as many questions as it does answers," he said. "Cell therapy attempts to repopulate the heart with new heart cells. But which cells should be used, and when they should be put into the heart are among many unanswered questions."
To address at least some of those questions, Houser's team plans next to investigate CBSCs in a large-animal heart attack model. If that study yields similar results as the first, the cells could be ushered into a small-scale clinical trial of human patients. In humans, CBSCs would be collected from bone using techniques akin to those employed for bone marrow aspiration, a much simpler process than that used to isolate cardiac stem cells. While the cells would originate from a different person, raising the risk of rejection by the patient's immune system, it may be possible to have them at the ready in hospital settings, allowing for their injection immediately after a heart attack.
The cell therapy work by Houser's team represents just one of several forms of heart therapy being explored at Temple's CVRC. According to Houser, "Temple has made a commitment to cardiovascular research, with a clinical enterprise focused on treating patients. We're trying anything and everything to repair the heart [safely]." Other avenues of research include gene therapy, drug therapy, and the use of novel biomaterials to more effectively deliver drugs.
Other researchers contributing to the work include Catherine A. Makarewich, Thomas E. Sharp, Timothy Starosta, Yumi Chiba, Remus M. Berretta, and Hajime Kubo, at the Cardiovascular Research Center at Temple; Nicholas E. Hoffman and Muniswamy Madesh, at the Center for Translational Medicine at Temple; and Fang Zhu, at the Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center.
The research was supported in part by NIH grants R01HL089312, T32HL091804, P01HL091799, and R37HL033921.
About Temple Health
Temple Health refers to the health, education and research activities carried out by the affiliates of Temple University Health System and by Temple University School of Medicine.
Temple University Health System (TUHS) is a $1.4 billion academic health system dedicated to providing access to quality patient care and supporting excellence in medical education and research. The Health System consists of Temple University Hospital (TUH), ranked among the "Best Hospitals" in the region by U.S. News & World Report; TUH-Episcopal Campus; TUH-Northeastern Campus; Fox Chase Cancer Center, an NCI-designated comprehensive cancer center; Jeanes Hospital, a community-based hospital offering medical, surgical and emergency services; Temple Transport Team, a ground and air-ambulance company; and Temple Physicians, Inc., a network of community-based specialty and primary-care physician practices. TUHS is affiliated with Temple University School of Medicine.
Temple University School of Medicine (TUSM), established in 1901, is one of the nation's leading medical schools. Each year, the School of Medicine educates approximately 840 medical students and 140 graduate students. Based on its level of funding from the National Institutes of Health, Temple University School of Medicine is the second-highest ranked medical school in Philadelphia and the third-highest in the Commonwealth of Pennsylvania. According to U.S. News & World Report, TUSM is among the top 10 most applied-to medical schools in the nation.
Jeremy Walter | EurekAlert!
How prenatal maternal infections may affect genetic factors in Autism spectrum disorder
22.03.2017 | University of California - San Diego
22.03.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
22.03.2017 | Materials Sciences
22.03.2017 | Physics and Astronomy
22.03.2017 | Materials Sciences