Although medical advances have extended the lifespans of DMD patients from their teens or 20s into their early 30s, disease-related damage to the heart and diaphragm still limits their lifespan.
“Almost 100 percent of patients develop dilated cardiomyopathy,” in which a weakened heart with enlarged chambers prevents blood from being properly pumped throughout the body, said University of Illinois comparative biosciences professor Suzanne Berry-Miller, who led the study. “Right now, doctors are treating the symptoms of this heart problem by giving patients drugs to try to prolong heart function, but that can’t replace the lost or damaged cells,” she said.
In the new study, the researchers injected stem cells known as aorta-derived mesoangioblasts (ADM) into the hearts of dystrophin-deficient mice that serve as a model for human DMD. The ADM stem cells have a working copy of the dystrophin gene.
This stem cell therapy prevented or delayed heart problems in mice that did not already show signs of the functional or structural defects typical of Duchenne muscular dystrophy, the researchers report.
Berry-Miller and her colleagues do not yet know why the functional benefits occur, but proposed three potential mechanisms. They observed that some of the injected stem cells became new heart muscle cells that expressed the lacking dystrophin protein. The treatment also caused existing stem cells in the heart to divide and become new heart muscle cells, and the stem cells stimulated new blood vessel formation in the heart. It is not yet clear which of these effects is responsible for delaying the onset of cardiomyopathy, Berry-Miller said.
“These vessel-derived cells might be good candidates for therapy, but the more important thing is the results give us new potential therapeutic targets to study, which may be activated directly without the use of cells that are injected into the patient, such as the ADM in the current study,” Berry-Miller said. “Activating stem cells that are already present in the body to repair tissue would avoid the potential requirement to find a match between donors and recipients and potential rejection of the stem cells by the patients.”
Despite the encouraging results that show that stem cells yield a functional benefit when administered before pathology arises in DMD mouse hearts, a decline in function was seen in mice that already showed the characteristics of dilated cardiomyopathy. One of these characteristics is the replacement of muscle tissue with connective tissue, known as fibrosis.
This difference may occur, Berry-Miller said, as a result of stem cells landing in a pocket of fibrosis rather than in muscle tissue. The stem cells may then become fibroblasts that generate more connective tissue, increasing the amount of scarring and making heart function worse. This shows that the timing of stem cell insertion plays a crucial role in an increase in heart function in mice lacking the dystrophin protein.
She remains optimistic that these results provide a stepping-stone toward new clinical targets for human DMD patients.
“This is the only study so far where a functional benefit has been observed from stem cells in the dystrophin-deficient heart, or where endogenous stem cells in the heart have been observed to produce new muscle cells that replace those lost in DMD, so I think it opens up a new area to focus on in pre-clinical studies for DMD,” Berry-Miller said.The Illinois Regenerative Medicine Institute supported this research.
Chelsey Coombs | University of Illinois
Further reports about: > ADM > DMD > Duchenne muscular dystrophy > X chromosome > cell membrane > connective tissue > dilated cardiomyopathy > heart function > heart muscle > heart muscle cells > heart problems > mouse model > muscle cells > muscle contraction > muscle tissue > muscle weakness > muscular dystrophy > stem cells
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
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...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences