A human stem cell model of muscular dystrophy

Drug discovery company Genea Biocells has demonstrated and described the world’s first human stem cell-based cellular model for a muscular dystrophy that is suitable for high-throughput screening and drug development.

Publishing their research in the journal Stem Cells Translational Medicine, the company’s scientists explained how they were able to analyse in detail cellular and molecular aspects of facioscapulohumeral muscular dystrophy (FSHD) during myogenic development and in myotube cultures by comparing muscle cells generated from five FSHD-affected and four normal control stem cell lines.

FSHD is an inheritable muscle disease affecting approximately one in 8000 people, slowly consuming their skeletal muscle. According to the study authors, the debilitating disease “represents a major unmet clinical need”, with the dearth of adequate experimental models severely hampering our understanding of it. There is no cure or treatment strategy for patients with FSHD.

“Human embryonic stem cells (hESCs) potentially represent a renewable source of skeletal muscle cells (SkMCs) and provide an alternative to invasive patient biopsies,” the researchers noted. With this in mind, they “developed a scalable monolayer system to differentiate hESCs into mature SkMCs within 26 days, without cell sorting or genetic manipulation”.

The findings highlight Genea Biocells’ efficient and scalable monolayer system to differentiate human pluripotent stem cells into SkMCs and demonstrate disease-specific phenotypes in muscle derived from both human embryonic and induced pluripotent stem cells affected with FSHD. Dr Uli Schmidt, Genea Biocells’ general manager and principal investigator of the project, said a range of cellular pathways involved in FSHD pathology were identified.

“Importantly,” he said, “we have demonstrated those in the world’s first ‘disease in a dish’ model of FSHD, which is a highly consistent, reproducible and scalable resource that provides many advantages over invasive patient biopsies.

“We believe that disease modelling using human stem cells inherently containing disease-inducing stimuli provides us with an invaluable edge throughout the drug development process. These cells are human, physiologically relevant and enable clinically relevant assay readouts for drug screening and further functional testing,” he added.

The study authors believe their cellular model will be “a powerful tool for studying FSHD and will ultimately assist in the development of effective treatments for muscular dystrophies”.