There Is Hope For Liver Regeneration Thanks To Organoids

The only other internal organ that is capable of self-regeneration is the liver. Even if seventy percent of the liver is destroyed, its tissue may recover into a fully functioning organ in a few of months. This is a remarkable fact. By deciphering the underlying processes that are responsible for this one-of-a-kind regenerating potential, researchers may be able to open up new therapy options for chronic liver illnesses in addition to organ transplantation. To this day, however, the reasons behind and mechanisms behind the liver's ability to repair itself remain a mystery.

Now, a group of bioengineers from the Massachusetts Institute of Technology headed by Arnav Chhabra have detailed a novel model of the liver in a work that was published in the Proceedings of the National Academy of Sciences. Researchers are now able to grasp the biological processes that are responsible for the regeneration of liver tissue thanks to a model that is built on a microfluidic chip. The model also identifies a number of compounds that may stimulate the process.

The development of a model of the liver that included three essential components—namely, hepatocytes, endothelial cells, and simulated blood flow—was the major objective of the work. Hepatocytes are the most common kind of cell to be found in liver tissue. Endothelial cells are the cells that line the inside of blood arteries and are responsible for regulating the movement of chemicals between the circulation and other tissues.

Endothelial cells have been shown in previous studies to play an important role in the process of liver regeneration. Endothelial cells are the source of proteins that hepatocytes, the cells that make up the liver, need to stimulate tissue development. Researchers have also uncovered the fact that blood flow is an essential component in the process of liver regeneration. Endothelial cells have their activity stimulated when there is an increase in blood flow, which results in an increase in the quantity of growth proteins that endothelial cells release into the liver.

Together with Christopher Chen, a professor of biomedical engineering at Boston University, the researchers used this information to build a microfluidic chip that could fulfil all of their requirements for a liver model. Chips used in microfluidic devices are typically made of materials such as glass or silicon and include tiny channels carved onto them. When liquid is introduced into the small tubes, researchers have the ability to quickly alter the pressure and flow of the liquid. This is especially helpful for cell culture research since it enables researchers to carefully regulate the fluid environment in which cells are produced.

They planned their chip to have two primary compartments that were linked together by a channel between them. These compartments and the channel held samples of human endothelial cells and fluid that was rich in nutrients. Fluid could be pumped to and from either compartment via the tiny central channel that was located between the two compartments. The researchers had a hypothesis that if they grew endothelial cells via the narrow central channel and pumped nutrient-dense fluid through the chip, they would be able to simulate the shape and function of a human blood artery.

The next step required the group to create a model of their liver tissue. The researchers placed a sliver of gel in the space between the two chambers of endothelial cells and then cut a passageway through the gel so that it would serve as the central channel. Researchers injected a combination of human hepatocytes and human fibroblasts into this gel. The gel was then placed in a petri dish. It was decided to incorporate fibroblasts in order to increase the likelihood that the liver cells would continue to survive. The nutrients from the model blood artery were able to penetrate outwards into the gel and reach the human liver cells because the liver cells were injected into the gel. This was very similar to how the nutrients would reach the human liver cells inside of the human body.

After the researchers had shown that their model was able to maintain the viability of both the liver hepatocyte cells and the endothelium cells, they were in a position to investigate the biological signals that were necessary to stimulate the expansion and regeneration of liver cells.

Previous research with mice found that the process of liver regeneration was accompanied by heightened levels of inflammatory proteins known as cytokines. In zebrafish, the process of liver regeneration was shown to be controlled by a protein known as prostaglandin E2. The researchers conducted separate trials in which they included cytokines and prostaglandin E2 into their nutrient-dense fluid in order to investigate the impact that these molecules have on the capacity of human liver cells to regenerate.

Prostaglandin E2 had an interestingly large impact on the process of cell regeneration in the liver. After being exposed to prostaglandin E2, the number of cells entering the cell cycle and producing new cells rose from 5 to 20%. This was the result of the liver cells. The same was true for the cytokine known as interleukin-1 beta. This raised a significant query: what is the connection between interleukin-1 beta and prostaglandin E2?

Interleukin-1a may enhance the production of prostaglandin E2, which may result in liver cell regeneration, according to the researchers' hypothesis. Chhabra et al. employed a technique called gene editing to test this hypothesis by preventing hepatocyte cells from producing the enzyme prostaglandin E synthase. Prostaglandin E synthase is an enzyme that is required for the production of prostaglandin E2 proteins. After that, the researchers used their liver model to test the effects of interleukin-1. Interleukin-1 did not result in liver cell regeneration when prostaglandin E2 was not present, as the researchers had anticipated. This finding was in accordance with their predictions. These findings substantiated the hypotheses that interleukin-1 drives the production of prostaglandin E2 and that prostaglandin E2 has the ability to stimulate liver cell regeneration in vitro.

These findings represent a substantial step forward in our capacity to comprehend the regeneration capabilities of the human body. We can only hope that when we find additional chemicals that play a role in human cell regeneration, this discovery may pave the way for alternate therapies for disorders that normally call for organ transplantation.