A research team led by Lecturer Hidetoshi Sakurai of CiRA and Akihito Tanaka, a graduate student at Nagoya University Graduate School of Medicine who is currently engaged in external research at CiRA has developed a technique for producing myocytes from human iPS cells which is superior to existing methods in efficiency, reproducibility, and speed.

iPS cells offer two great potentials. One is the possibility of generating iPS cells from the patient and using them to reproduce patient pathologies at cellular level in vitro. This should make it possible to screen a wide range of drugs for efficacy, leading to the development of therapeutic options. The other potential is that cells differentiated from iPS cells could be used to restore cell functions lost through injury or illness. Regenerative medicine based on cell transplantation is also a promising prospect.

The first step toward realizing these potentials is to develop a method that ensures a stable supply of high-quality differentiated cells. However, the methods of inducing skeletal muscle cells from human iPS cells reported so far have been associated with a range of issues. For instance they may be complex and time-consuming, or have poor levels of reproducibility, or low rates of efficiency. To remedy these issues, researchers have worked to develop new methods of skeletal muscle differentiation.

In the study reported here, expression of the transcription factor MyoD1, which is known to convert cell fate to a skeletal muscle cell lineage, was induced in human iPS cells, resulting in successful production of skeletal muscle cells with an efficiency rate of around 90%. This protocol was then used to generate myocytes from two iPS cell lines derived from a patient with Miyoshi muscular dystrophy. It was confirmed that, when a hole was opened at one point on the membrane of these cells by laser irradiation, the speed of repair was slower than in cells from healthy subjects. Miyoshi muscular dystrophy patients are known to be deficient in the membrane protein dysferlin, but membrane repair functions were found to be restored when the dysferlin gene was overexpressed in the cells.

Using the method of myogenic differentiation developed in the study, the researchers were able to establish a stable supply of myocytes and to create a system to detect the healing of the cell membrane. Going forward, this method should find applications in drug screening. The findings of the study were published at 5:00 PM on April 23, 2013 (US Eastern time) in the online scientific journal PLOS ONE.

• doi: 10.1371/journal.pone.0061540