Researchers here report on the use of 3-D printing techniques to generate small, functional liver organoids from patient-derived cells. A cell sample is reprogrammed into induced pluripotent stem cells, and these are then differentiated into liver cell clusters to be used in the printing process. These organoids lack a vasculature, and thus cannot be made larger than a few millimeters in size. Given the progress made by Lygenesis and other groups towards the practical use of liver organoids even without vasculature, however, by implantation into lymph nodes, or into the liver itself, patients may well benefit considerably in the near future.
Using human blood cells, researchers have succeeded in obtaining hepatic organoids ("mini-livers") that perform all of the liver's typical functions, such as producing vital proteins, storing vitamins, and secreting bile, among many others. The innovation permits the production of hepatic tissue in the laboratory in only 90 days and may in the future become an alternative to organ transplantation. This study combined bioengineering techniques, such as cell reprogramming and the cultivation of pluripotent 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.
"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." The innovative part of the study resided in how the cells were included in the bioink used to produce tissue in the 3D printer. Instead of printing individualized cells, researchers 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.
The researchers thereby avoided a problem faced by most human tissue bioprinting techniques, namely, the gradual loss of contact among cells and hence loss of tissue functionality. Spheroid formation in this study already occurred in the differentiation process, when pluripotent cells were transformed into hepatic tissue cells (hepatocytes, vascular cells, and mesenchymal cells). Researchers started the differentiation process with the cells already grouped together. They were cultured in agitation, and groups formed spontaneously.