A recent study has shown that muscle stem cells called mesoangioblasts can be grown in the laboratory from induced pluripotent stem cells (IPS cells). Scientists think that mesoangioblasts transplants may be an effective treatment for muscular dystrophy but currently these cells have to be taken from donor who is a tissue ‘match’ for the patient, which is relatively rare.As IPS cells are grown in the lab from a patient’s own muscle cells this could potentially overcome the problem of having to find a ‘matched’ donor. In this study researchers grew mesoangioblast-like cells from patient derived IPS cells. They then genetically corrected these cells and transplanted them into mice with Limb-girdle muscular dystrophy type 2D. After the transplant mice produced some healthy muscle cells and gained muscle strength. Researchers hope that in the future this technique might be used in cell based therapies for human muscular dystrophies.
What is the idea behind this study?
Muscular dystrophies are a group of genetic muscle wasting diseases. Scientists hope that if stem cells can be delivered to patients’ muscles they could grow healthy muscle fibres and prevent further muscle wasting. Mesoangioblasts are a type of stem cell found in skeletal muscles. Scientists think they might be a good candidate for stem cell therapy because, unlike other types of muscle stem cell, they survive well and can move across blood vessel walls into muscle tissue after injection into the bloodstream.
Recently mesoangioblasts from healthy donors have been used in a clinical trial to treat Duchenne muscular dystrophy. To prevent the patients’ immune systems from attacking these donor cells they had to be taken from siblings who were a tissue ‘match’. Unfortunately matched donors are not available for every child, limiting the number who can potentially be treated.
To avoid having to use donor cells, scientists had hoped to isolate mesoangioblasts from patients and genetically correct them in the laboratory before giving then back to the same patient. Unfortunately they found patients’ muscles didn’t contain enough mesoangioblasts to be used in any potential treatment. Instead scientists in this study aimed to grow mesoangioblasts in the laboratory from induced pluripotent stem cells before genetically correcting them and looking for possible affects in mice with limb-girdle muscular dystrophy type 2D.
What did this study show?
Scientists took muscle cells from healthy individuals and limb-girdle muscular dystrophy type 2D patients and reprogrammed them to become induced pluripotent stem (IPS) cells. They then developed a process to successfully grow mesoangioblast-like cells from these IPS cells in the laboratory. These mesoangioblasts could form muscle fibres and did not form tumours when transplanted into mice.
In limb-girdle muscular dystrophy type 2D a genetic fault stops muscle cells producing a protein called α-sarcoglycan, so next researchers used a virus to genetically correct these mesoangioblast-like cells so that they produced normal α-sarcoglycan protein. When these cells were injected into dystrophic mice they moved to damaged muscles where they formed some new, healthy muscle fibres which produced α-sarcoglycan. However this process was not very efficient, perhaps because human cells were being used in a mouse.
Finally to measure how effective this type of treatment might be, scientists created mesoangioblast- like cells from healthy mouse IPS cells. When injected into dystrophic mice these were much more effective than human cells, forming many more healthy muscle fibres. After this treatment mice gained muscle strength and could exercise for longer.
What does this mean for patients?
This study has provided scientists with a method to grow mesoangioblast-like cells from induced pluripotent stem cells in the laboratory. IPS cells are ‘immortal’ so an unlimited number of these mesoangioblast-like cells could potentially be grown from a patient’s own skin cells. Genetic correction of these cells appears to be safe and somewhat effective to treat mice with limb-girdle muscular dystrophy type 2D. This is a promising avenue for the treatment of this and other muscular dystrophies in humans in the future.
However much further work is needed before these advances can be turned into new muscular dystrophy therapies. As this work was done in mice, scientists don’t know whether it will be effective in humans and further safety checks would be needed before any clinical trial could take place. Both the production of IPS cells and the process of growing mesoangioblast like cells from them are hugely inefficient. Cell based therapies will require large numbers of cells in order to target all the muscles in the body, so scientists need to improve the efficiency of the process in order produce enough of these cells to treat patients.
Further information and links
- The full original paper in the journal Science Translational Medicine (published June 2012, may require journal subscription)
- EuroStemCell fact sheet giving an overview of stem cell research on muscular dystrophy
- More information for patients from the Muscular Dystrophy Campaign
- More about OptiStem, the EU-funded research project behind this summary
This summary was written by Rachel Gill, BSc. Funding from the European Community’s Seventh Framework Programme project OPTISTEM supported this scientific work and summary.
Updated by: Jan Barfoot