A remarkable new step toward heart regeneration: a beating 3D micro heart from induced pluripotent stem cells.
This is what a new study by Dr. Bruce Conklin’s lab at the Gladstone Institute of Cardiovascular Disease and the University of California, San Francisco described in a new manuscript published in the journal Scientific Reports.
Engineering micro heart muscle from induced pluripotent stem cells has been challenging: obtaining aligned and unidirectionally contracting tissue without requiring unfeasibly high numbers of cells and requiring easily manufactured materials has been a traditional constraint that has limited progress in this area. Moreover, differentiating iPS cells into heart cells produces weak and immature heart cells, making working with these cells difficult.
The new study overcame these constraints by creating a system wherein the authors seeded a mixture of cardiomyocytes and fibroblasts derived from iPS cells into stencils containing – in the authors’ own words – “dogbone” through-holes comprised of a high-aspect ratio “shaft” flanked on either end by square “knobs.”
To clarify this design, see image in Panel A below.
Such confinement of cardiomyocytes and fibroblasts into rectangular canals aligned in three dimensions and induced uniaxial beating within these canals.
Moreover, such alignment allowed the authors to work with significantly fewer cells than traditionally needed for engineered micro heart tissue systems.
This is a remarkably simple solution to a complex problem.
These cells were also cultured for a short time, during which they adopted an in vivo-like morphology, and exhibited some functional aspects of adult cardiac tissue. These paramters, however, require further investigation and experimentation.
The authors intend to follow this up with more advanced systems that allow parallelization and automation, to try and achieve a higher throughput screening system of artificial mini hearts.
See video below of the beating mini hearts in action.
And though more work is necessary to establish whether this iPS-CM-based micro heart system can accurately model adult heart tissue, it is an interesting example of how geometry and environment can regulate the behavior of cells and tissue towards fully functional organs.