Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stem cells of limited use for cardiac muscle repair

02.12.2004


New evidence suggests that a promising investigational treatment for patients with damaged hearts -- using adult stem cells to regenerate heart tissue -- may not work as planned. In the December 2004 issue of the Journal of Clinical Investigation, researchers from the University of Chicago show that although stem cells derived from bone marrow can find their way to areas of damaged heart muscle, infiltrate into these regions and proliferate, they do not mature into new cardiac muscle cells.

A series of previous studies suggested that stem cells from bone marrow could be induced to become cardiac muscle, replacing damaged tissue and potentially restoring heart function. This series of more-rigorous experiments, however, found that the transplanted cells are unable to take the crucial final steps. They do not produce a muscle protein called sarcoglycan, which is necessary for normal heart and skeletal muscle function.

The failure of these cells to express this protein "severely limits their utility for cardiac and skeletal muscle regeneration," the authors note. "This was a complete surprise, and a considerable disappointment," said study director Elizabeth McNally, M.D., Ph.D., associate professor of medicine at the University of Chicago. "We set out to confirm, using more stringent criteria, the very appealing strategy of using stem cells from bone marrow to regenerate cardiac muscle, but we found that they never become normal, mature muscle cells."



The researchers used bone marrow side population cells (BM-SP), a sub-set of the stem cells found in marrow. Earlier studies demonstrated that these cells could home in on areas of damaged muscle and suggested that they matured into working skeletal or cardiac muscle cells. Clinical trials of this approach are already underway in patients who have had a heart attack and initial results have been "promising."

Despite high hopes for such cellular self-renewal, however, many researchers remained skeptical about the capacity of adult stem cells, even BM-SP cells, to complete the transition. McNally, a cardiologist who studies the genetics of muscle disease, realized that mice in her lab that lack a receptor called g-sarcoglycan, normally found on the surface of muscle cells, provided the perfect test of this approach. Mice born without a functioning g-sarcoglycan gene have multiple tiny heart attacks that produce "microinfarcts," small regions of degeneration. So McNally and colleagues collected BM-SP cells from normal male mice and injected them into female mice that lacked sarcoglycan. By tracing the male Y chromosomes -- found only in the donated BM-SP cells -- they discovered that the injected cells located the areas of muscle damage and insinuated themselves, sometimes as separate cells and sometimes by fusing with muscle cells.

In neither case, though, did they produce sarcoglycan, a reliable marker of mature muscle cells. When the researchers repeated the experiment with whole bone marrow, rather than isolated BM-SP cells, they got identical results.

They were slightly more successful with skeletal muscle. After examining 10,000 muscle fibers from each of 14 mice they found two myofibers that contained sarcoglycan. These results are difficult to reconcile with the promising responses seen in mice and humans treated with adult stem cells. "It’s clear that the transplanted cells aren’t growing, as we once hoped, into heart cells," McNally said, "but they may stimulate the growth of new blood vessels into the damaged regions or they may secrete growth factors that promote recovery." If we can figure out what is actually going on in these patients and understand the mechanism, she added, we might be able to design a more effective approach.

The next step may be to find more flexible sources of injectable cells. Although readily available, BM-SP cells appear to have limited potential. Several researchers are trying to isolate a putative cardiac stem cell, which could mature into functional heart muscle. Embryonic stem cells also are an option. "The whole idea of regenerative cellular medicine is very attractive," said McNally. "Many of the diseases that most concern us involve degeneration of the heart or the brain. The notion of replacing those cells has a lot of appeal. But it does not look like stem cells from bone marrow are going to make that realistic for patients with heart failure any time soon."

John Easton | EurekAlert!
Further information:
http://www.uchospitals.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>