Chemical engineers from the University of Toronto have created a set of mini-bioreactors that act as a kind of training gym to turn human stem cells into functional heart tissue. And like any training regimen, they’ve discovered that pushing the cells to their limits yields better results.
Because mature cardiomyocytes (heart muscle cells) rarely divide, the only way to grow them in the lab is from stem cells. But tissues grown this way tend to have immature characteristics. “Cardiomyocytes start off as small, oval cells, which during development turn into rectangular, brick-shaped cells that are much larger in size,” says Milica Radisic, a chemical engineering professor at U of T’s Institute of Biomaterials & Biomedical Engineering. Current lab-grown cells lack this shape, along with other characteristics such as high electrical conductivity and efficient calcium transport mechanisms.
In a new protocol recently published in Nature Methods, Radisic’s team suspended a surgical suture made of silk above a long thin channel made of polydimethylsiloxane (PDMS), which was bathed in a cell culture medium. The channel was seeded with stem cells and other support cells, which over the course of several days grew into a heart tissue fibre that enveloped the silk suture. This ‘biowire’ was then subjected to pulsed electrical current, as in a pacemaker. The idea was to mimic conditions inside a growing fetal heart, which ramps up to 180 beats per minute over the course of nine months. However, to their surprise the team found that the best results — the most mature and adult-like heart cells — were obtained by pushing the cells from 60 to 360 beats per minute over the course of only a week. “It’s like boot camp, versus going to the gym every day for a little bit,” says Radisic.
Radisic says there is already interest from pharmaceutical companies in using her more mature cells to test new heart drugs. But the ultimate goal, still years away, would be to collaborate with doctors and use lab-grown fibres to repair damaged hearts in humans.