Video: Mini 3D human hearts made from scratch

In the dish, they’re just tiny dots. But look through a microscope and you can see minute beating human hearts, each sporting its own ventricle-like chamber.

The tiny organs measure about half a millimetre in diameter, with the “hump” of the ventricle rising up from the dish. It’s the first time that three-dimensional heart-like organs have been created from stem cells alone.

“It’s impossible to see the contraction with the naked eye, and that’s why we call them micro-hearts,” says Zhen Ma of the University of California at Berkeley.

Such organs have been built before, but only with the help of pre-existing structures to hold the new cells in place – such as the collagen matrix left after a donor heart has been stripped of its cells or made with a 3D printer.


You can’t grow here

Ma used induced pluripotent stem cells to form the organs, created by rewinding ordinary human skin cells back to a primordial, embryonic-like state.

Researchers normally use growth factors alone to persuade such stem cells to form the specialised cells of an organ, but Ma’s team used an extra trick. To mimic the physical forces that usually tell fetal stem cells where they can or can’t grow, they etched chemical “no-go” zones, creating wells in the dish. These forced the stem cells to collect in the right configuration.

This process changed their shape, imitating what happens when real hearts form in developing embryos. As a result, those in the centre of the wells turned into beating heart cells called cardiomyocytes. These were surrounded by skin-like cells called fibroblasts, which form the heart’s connective tissue. Most strikingly, the cardiomyocytes also grew upwards to form dome-like cavities that resembled microscopic ventricles.

Free-standing hearts

The ultimate aim is to construct a full-size organ. “Our model is the first step towards building a heart relying on self-organisation of cells, without any external three-dimensional supporting materials,” says Ma.

More immediately, the micro-hearts may be useful for screening and identifying chemicals and drugs that could cause heart defects as fetuses develop in the womb. For example, in its current work, the team showed that the micro-hearts didn’t develop properly if exposed to thalidomide, a drug that infamously resulted in birth defects when pregnant women took it to treat morning sickness.

Uncharted ground

The approach could be applied to other three-dimensional micro-organs. Mini brains, kidneys, eyeballs, breasts and liver buds have been made in the lab before. Unlike the micro-hearts, these are made from random clumps of cells called organoids which make them less like the real thing.

Understanding the role of biomechanical forces during organ formation is the next big hurdle in getting stem cells to differentiate into the cells you want, says Harald Ott, of Massachusetts General Hospital in Boston, who is working on creating tissue-engineered limbs. “This study nicely ventures into these uncharted grounds. It beautifully recapitulates early stages of structure formation during heart development.”

Journal reference: Nature Communications, DOI: 10.1038/ncomms8413