Researchers at Duke University have created working muscle cells from pluripotent stem cells opening up the possibility of developing new treatments for muscular diseases.
The study of diseases such as muscular dystrophy is difficult in a laboratory setting due to problems developing and maintaining functional muscle tissue. If muscle tissue can be grown from stem cells and be maintained for weeks or months, it could prove invaluable to researchers and be instrumental in advancing understanding of muscular diseases.
If 2-dimensional and 3-dimensional muscle models could be developed with fully functional features from diseased cells harvested from patients, it would be possible to test the effectiveness of certain drugs and develop tailored treatments to halt or even eliminate the disease.
Due to the ethical issues over the use of embryonic stem cells, iPS cells are most commonly used by researchers. iPS cells can also be easily created from the cells of specific patients which would allow tailored treatments to be developed.
The team used skin stem cells harvested from patients, which were converted back to their immature state. The induced pluripotent stem cells were then converted to muscle cells using a carefully controlled chemical system. The resultant muscle tissue contracted when subjected to electrical signals and displayed far greater functionality than previous attempts to grow muscle tissue in the lab.
Muscle cells need to be grown on an extracellular matrix in a carefully controlled environment and there is a tendency for the muscle cells to detach from the extracellular matrix over time – usually within 10 days.
The reason for this is immature muscles fibers twitch during development which helps achieve fusion and maturation. However, the twitching causes immature muscle fibers to detach from the extracellular matrix, and once detached, they cannot be maintained in a culture.
The researchers developed a new method of culturing, incubating, and maturing the cells that produced far better results. By growing the cells in a 3D matrix, when the muscle fibers twitched, the ECM moved with them preventing them from detaching. Using the new technique, the researchers increased the culture time from 10 days to five weeks.
The researchers note that the tissue they created, while representing a major advance, more closely resembled fetal muscle tissue and lacked the contractile strength of adult muscle tissue. Consequently, the lab-grown muscle tissue would not be suitable for transplanting into patients, but there is potential for use in drug testing and the study of disease. Other members of the team used their technique to develop iPS cells into heart muscle cells which were used in a heart patch that had the same contractile strength as adult heart muscle tissue.
The team is still fine tuning its system, but the advances made so far raise hopes that it will soon be possible to develop a fully functional muscle model for use in medical research and drug testing.