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Stem cell mechanobiology for heart regeneration

Dr Yu Suk Choi, Institution: University of Western Australia

2016 Future Leader Fellowship

Years funded: 2017-2021


Stem cells hold great promise to repair/regenerate damaged tissue, particularly relevant to the failing heart. Surprisingly to date, more than 10 international clinical trials have failed to successfully convert stem cells into functional heart muscle cells. Previous studies suggested that delivered stem cells were either too naïve or trans-differentiated to unwanted lineages e.g. calcified bone. This project is approaching the problem in a new way by focussing on the stem cell microenvironment.

Stem cells sense how soft or stiff the underlying matrices on which they are grown are. This conversion of mechanical sensing to biochemical signalling, known as mechanotransduction, has recently been shown to be critical in determining a stem cell’s fate. Stem cells can be driven to differentiate into brain-, muscle-, and bone-like cells on hydrogels that mimic stiffness of tissues of origin, independently of biochemical supplement. Here, we propose to develop ‘smart hydrogel’ platforms with the capacity of promoting heart muscle cell formation from stem cells. This project will explore whether raising stem cells in an environment that mimics biophysical properties of heart tissue has a greater potential for success at heart muscle cell generation, with a view to producing the optimal microenvironment for stem cells derived from fat to succeed in cardiac repair and to generating ideal heart muscle cells for future clinical trials.

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