Scientists create functional ‘mini-livers’ with 3D printing technology

Artificial organs could provide the solution to many problems caused by traditional organ transplantation. Complications such as lack of organ availability and issues surrounding organ rejection could be avoided thanks to 3D bioprinting technology.

Using human blood cells, Brazilian researchers have successfully created hepatic organoids ('mini-livers') that perform all of the liver's typical functions, such as producing vital proteins, storing vitamins, and secreting bile. This innovate process that permits the production of hepatic tissue in laboratory conditions takes just 90 days to complete and may in the future become an alternative to organ transplantation.

Bioprinting is a promising technology, it refers to generating custom organs and tissues unique to each patient by using their own cells. This is a complex process as living organs have intricate structures, but a team of scientists from the Centre for Stem Cell and Human Genome Research (HUG-CELL) at the University of São Paulo, Brazil, have made some promising breakthroughs with bioprinting. 

The production of the ‘mini-liver’ is not the first time that tissue has been produced using 3D technology, but previous attempts have seen cell functionality reduce quickly. This study combined bioengineering techniques, such as cell reprogramming and the cultivation of pluripotent (‘master cells’) stem cells, with 3D bioprinting. Thanks to this strategy, the tissue produced by the bioprinter maintained hepatic functions for longer than reported by other groups in previous studies.

A liver in 90 days

According to the researchers, the complete process from collection of a patient's blood to functional tissue production takes around 90 days and can be divided into three stages: differentiation, printing, and maturation.

The first step is to culture the patient's blood cells into induced pluripotent stem cells. Japanese scientist Shinya Yamanaka was awarded the 2012 Nobel Prize for Medicine for developing this technique.

The second stage involves inducing differentiation into liver cells. The cell structures known as ‘spheroids’ are then mixed with bioink, a hydrogel-like fluid, and printed out. The resulting structures mature in culture for 18 days.

Lead HUG-CELL researcher Ernesto Goulart said: "We started the differentiation process with the cells already clustered. They were cultured in agitation, and the groups formed spontaneously. Once obtained, the spheroids were mixed with a bioink - fluid similar to hydrogel - and printed. The resulting structures undergo a maturation process in culture for 18 days.”

Although this study was limited to producing miniature livers, the technique is promising and could be used in the future to produce complete organs suitable for transplantation, according to Goulart.

"In the very near future, instead of waiting for an organ transplant, it will be possible to take cells from the patient and reprogram them to produce a new liver in the laboratory," says Mayana Zatz, director of HUG-CELL. 

Reference: Goulart et al 2019 3D bioprinting of liver spheroids derived from human induced pluripotent stem cells sustain liver function and viability, in vitro Biofabrication 12 015010

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