3D Printed Mini Livers

Using human blood cells, Brazilian 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.
The study was conducted at the Human Genome and Stem Cell Research Center (HUG-CELL). Hosted by the University of São Paulo (USP), HUG-CELL is one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP.

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,” said Mayana Zatz, director of HUG-CELL and last author of the article published in Biofabrication.

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, 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,” said Ernesto Goulart, a postdoctoral fellow in USP’s Institute of Biosciences and first author of the article. 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). “We started the differentiation process with the cells already grouped together. They were cultured in agitation, and groups formed spontaneously,” Goulart told Agência FAPESP.

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

In this study, researchers developed mini-livers using blood cells from three volunteers as raw material and compared markers relating to functionality, such as the maintenance of cell contact and protein production and release. “Our spheroids worked much better than those obtained from single-cell dispersion. As expected, during maturation, the markers of hepatic function were not reduced,” Goulart said. Although the study was limited to producing miniature livers, the technique can be used in the future to produce complete organs suitable for transplantation, according to Goulart. “We did it on a small scale, but with investment and interest, it can easily be scaled up,” he said.

The article can be retrieved from iopscience.iop.org/.

Source: http://agencia.fapesp.br/

Nanomachines To Deliver Cancer Drugs to Hard-to-reach Areas

In a recent study in mice, researchers found a way to deliver specific drugs to parts of the body that are exceptionally difficult to access. Their Y-shaped block catiomer (YBC) binds with certain therapeutic materials forming a package 18 nanometers wide. The package is less than one-fifth the size of those produced in previous studies, so can pass through much smaller gaps. This allows YBCs to slip through tight barriers in cancers of the brain or pancreas.

The fight against cancer is fought on many fronts. One promising field is gene therapy, which targets genetic causes of diseases to reduce their effect. The idea is to inject a nucleic acid-based drug into the bloodstream — typically small interfering RNA (siRNA) — which binds to a specific problem-causing gene and deactivates it. However, siRNA is very fragile and needs to be protected within a nanoparticle or it breaks down before reaching its target.

siRNA can switch off specific gene expressions that may cause harm. They are the next generation of biopharmaceuticals that could treat various intractable diseases, including cancer,” explained Associate Professor Kanjiro Miyata of the University of Tokyo, who jointly supervised the study. “However, siRNA is easily eliminated from the body by enzymatic degradation or excretion. Clearly a new delivery method was called for.”

Presently, nanoparticles are about 100 nanometers wide, one-thousandth the thickness of paper. This is small enough to grant them access to the liver through the leaky blood vessel wall. However some cancers are harder to reach. Pancreatic cancer is surrounded by fibrous tissues and cancers in the brain by tightly connected vascular cells. In both cases the gaps available are much smaller than 100 nanometers. Miyata and colleagues created an siRNA carrier small enough to slip through these gaps in the tissues.

We used polymers to fabricate a small and stable nanomachine for the delivery of siRNA drugs to cancer tissues with a tight access barrier,” said Miyata. “The shape and length of component polymers is precisely adjusted to bind to specific siRNAs, so it is configurable.”

Source: https://www.u-tokyo.ac.jp/