Student Profile

Diogo Mosqueira

New insights into genetic disease using 3D engineered heart tissue made from human
pluripotent stem cell cardiomyocytes.

PhD Supervisor(s): Chris Denning; James Smith; Thomas Eschenhagen (Hamburg, Germany).


PhD Summary

The heart has minimal capacity to regenerate. This poses real challenges when it comes to understanding how genetic disease and drugs affect heart survival and function, and ultimately patient death. The species differences present between animal models and humans means the relevance of e.g. mice and rats to human pathophysiology is often difficult to interpret or even misleading. It is occasionally possible to obtain heart biopsies from patients. However, most biopsies are obtained during heart bypass surgery and taking repeat biopsies is neither ethical nor feasible. In addition, heart cells (cardiomyocytes) do not proliferate in culture and making established cell lines is not possible. A complete rethink is needed.

Human pluripotent stem cells (hPSCs) offer a new and potentially unlimited source of cardiomyocytes. Over the last 12 years, Chris Denning’s lab has developed culture and differentiation systems that allow high purities of cardiomyocytes to be derived from hPSCs [1,2,3]. These systems can be automated on our bespoke Tecan robotics platform. This allows pipeline production of hPSC-cardiomyocytes that can be scaled up in 92cm2 Robo-flasks for use in regenerative medicine or in vitro biomedical assays. The latter includes seeding cardiomyocytes into tissue engineered constructs, into 96- and 384-well assay plates for use on our new confocal pate reader or into high content automated electrophysiology platforms for assessing drug response.

These advances mean that it is now possible to consider engineering more complex 3D structures that allow simultaneous measurement of hPSC - cardiomyocyte contraction and function for in vivo and in vitro biomedical application.

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