Mini Human Organs Just Got Much Closer to Matching the Real Thing

Miniature organs have a new lifeline. Mimicking the way early human embryos grow blood vessels, scientists nudged multiple types of mini organs to sprout their own vascular networks.

Also called organoids, mini organs capture the intricacies of their natural organ counterparts, including how they grow, communicate, and function. This makes them perfect for research into genetic diseases and testing new drugs. Mini brains, for example, have already shed light on glioblastoma, a deadly brain cancer, and decoded how the brain controls muscles.

Organoids can also help parse genetic and developmental disorders. They carry the same genes as their donors—mini organs are often developed from skin cells—and can mimic a wide range of inherited diseases. They’re especially useful for charting the first stages of human development and can help tease out when and where things go wrong.

Despite their potential, mini organs have been haunted by one problem: They don’t have circulation. Without vessels to provide oxygen and nutrients and to wash waste away, mini organs can only develop so much. Over time, their core eventually dies, and they wilt away.

By analyzing mini organs and teasing out the genes and proteins involved in making vessels, the teams behind two new studies discovered multiple chemical cocktails to spur mini hearts, livers, lungs, kidneys, and intestines to naturally sprout forests of blood vessels.

Thanks to a steady infusion of nutrients, the upgraded organoids grew into some of the most complex mini organs to date. They developed structures and cells never seen before in the lab.

The techniques are likely universal and could generate other mini organs with blood vessels.

A Bloody Problem

Blood is often called the “elixir of life” for good reason: It nourishes the whole body with the delivery of oxygen and nutrients. Cut off blood supply, and most organs fail.

Organoids are the same. These mini organs usually begin life as skin cells, which are then chemically transformed into a stem-cell-like state. Protein cocktails nudge these cells into a variety of mini organs over the course of a few weeks gently churning in a bioreactor.

With the right concoction, the stem cells automatically form intricate 3D structures, such as mini brains resembling the second trimester of human fetal brain development. These organoids have similar types of brain cells to their natural counterparts distributed throughout and spark with electrical activity. Some even pump out anti-stress hormones when implanted into mouse brains, suggesting they might one day replace damaged tissues.

But lack of blood supply limits organoid development. There are already a few solutions. One is to embed organoids and endothelial cells—cells that line blood vessels—into a gel so both cell types develop together. Another uses 3D bioprinting to “write” vessel networks into small nubs of liver and heart organoids. Though they’re promising, both methods add complexity.

Humans, in contrast, automatically develop blood vessels that weave around and inside our organs as we develop in the womb. Why not recreate that process in a dish?

Pumping Blood

As an embryo develops, it separates into layers, each of which eventually transforms into a different organ. Blood vessel and heart cells originate in a layer called the mesoderm.

In one of the new studies, a Stanford team created glow-in-the-dark human stem cells in three colors to mark different types of heart and blood vessel cells. They made a pool of baby cardiovascular cells—which could become both heart and vessel cells—and added a cocktail of molecules and proteins, or growth factors, to nudge these into a heart with blood vessels.