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
In focus: Peptides, the “little brothers and sisters” of proteins
12.11.2018 | Technische Universität Berlin
How to produce fluorescent nanoparticles for medical applications in a nuclear reactor
09.11.2018 | Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly
The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...
Scientists developed specially coated nanometer-sized vehicles that can be actively moved through dense tissue like the vitreous of the eye. So far, the transport of nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. The work was published in the journal Science Advances and constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.
Researchers of the “Micro, Nano and Molecular Systems” Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, together with an international...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
12.11.2018 | Life Sciences
12.11.2018 | Materials Sciences
12.11.2018 | Physics and Astronomy