Bioengineered platforms for the measurement of force production of single hiPSC-cardiomyocytes in Duchenne Muscular Dystrophy cardiomyopathy

Duchenne Muscular Dystrophy is a X-recessive genetic disease affecting 1 in 3500 boys, culminating with cardiac failure around age 30. This disease results from more than 200 possible mutations on a single gene coding for the dystrophin, an important structural protein linking the intracellular skeleton to the extracellular matrix. Such dystrophin deficiency readily generates severe muscle degeneration during the first years of life, while cardiac symptoms appear abruptly only later, with dilation of the cardiac ventricle and contractile dysfunction affecting the pumping capacity of the heart.

For many years, cardiovascular research has been limited by the lack of appropriate in-vitro models. Human cardiac tissue and cells are scarce and cannot be maintained in culture for long periods, while animal models fail to recapitulate many aspects of the human heart biology.

To study the cellular mechanisms involved in the onset and progression of this disease, we combine two novel technologies: cardiac cells from patient-derived induced pluripotent stem cell (hiPSC) and bioengineered micropatterned hydrogel platforms. The later enable the measurement of force production of single cardiomyocytes under controlled microphysiological conditions, while the former offers unprecedented insights in the disease cellular biology using human isogenic cell line, with dystrophin mutations introduced or corrected using CRISPR/Cas9.

In this talk, I will present preliminary results as well as current efforts in our study of the molecular and biomechanical mechanisms involved in Duchenne Muscular Dystrophy cardiomyopathy.

Biography:
Born in Switzerland, Dr. Gaspard Pardon graduated with a MSc in Microengineering from EPFL in 2008, after which he moved to KTH Royal Institute of Technology in Stockholm, Sweden, where he obtained a PhD in Electrical Engineering - Micro and Nanosytems in 2014. The focus of his graduate work was on the engineering of novel micro- and nanofluidic technologies for point-of-care diagnostics with a special focus on electrokinetic phenomena in fluids, polymer engineering, and surface control and modification.

After a first postdoctoral experience at KTH, he moved to Stanford University for a postdoc supported by the Swiss National Science Foundation (SNF). After two years in the Microsystems and Mechanobiology laboratory of Prof. Beth L. Pruitt where he worked on microengineered platforms and hiPSC-cardiomyocytes as in-vitro cardiac models, he joined the Baxter Laboratory for Stem Cell Biology of Prof. Helen M. Blau where he applies his technology to the study of genetic cardiomyopathies.