By utilizing human blood cells, a team of researchers from the Human Genome and Stem Cell Research Center (University of São Paulo, Brazil) has successfully bioprinted hepatic organoids, in under 90 days.
Described in Biofabrication, the ‘mini-livers’ are reportedly capable of performing all hepatic functions, not limited to the production of proteins, vitamin storage and the secretion of bile. The team claims that this innovation may be the next step towards developing a personalized alternative to organ transplantation.
Mayana Zatz, Professor at the University of São Paulo, explained:
More stages have yet to be achieved until we obtain a complete organ, but we’re on the right track to highly promising results. In the very near future, instead of waiting for an organ transplant, it may be possible to take cells from the patient and reprogram them to make a new liver in the laboratory. Another important advantage is zero probability of rejection, given that the cells come from the patient.”
In describing the innovative part of their work, Postdoctoral Fellow and first author of the paper, Ernesto Goulart (University of São Paulo) continued:
Instead of printing individualized cells, we developed a method of grouping them before printing. These ‘clumps’ of cells, or spheroids, are what constitute the tissue and maintain its functionality much longer.”
We started the differentiation process with the cells already grouped together. They were cultured in agitation, and groups formed spontaneously.”
The printing process entails the deposition of spheroids along three axes, which is necessary for the material to gain volume and give the tissue proper support,” Goulart said. “The gel-like bioink is crosslinked to make the structures more rigid so that they can be manipulated and even sutured.”
It’s a somewhat traumatic process for the cells, which need time to get used to the environment and acquire functionality,” Goulart further explained. “At this stage, they aren’t tissue yet because they’re dispersed, but as shown by our study, they already have the capacity to clear the blood of toxins and to produce and secrete albumin [a protein produced only by the liver], for example.”
Blood cells were taken from three volunteers in this study and were compared to markers relating to function, as Goulart continued:
Our spheroids worked much better than those obtained from single-cell dispersion. As expected, during maturation, the markers of hepatic function were not reduced.”
Looking ahead, the team commented that while this particular study focused on their work with mini-livers, there is little stopping the team from scaling up their project to investigate printing complete organs for transplantation.
Sources: Goulart E, des Caires-Junior LC, Telles-Silva KA et al. 3D bioprinting of liver spheroids derived from human induced pluripotent stem cells sustain liver function and viability in vitro. Biofabrication. 12(11); http://agencia.fapesp.br/researchers-create-functional-mini-liver-by-3d-bioprinting/32217/