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 Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>