Massachusetts Institute Technology Researchers Developing Artificial Liver

Research towards creating artificial liver

10:55 AM, 3rd June 2013
MIT  Research News
MIT researchers have generated mature liver cells from induced pluripotent stem cells. In this image, the cell nuclei are stained blue. The green stain identifies liver cells, and the red stain identifies cells that are actively dividing.

MASSACHUSETTS, US: According to Sangeeta Bhatia, Engineer, Massachusetts Institute of Technology, the liver can indeed regenerate itself if part of it is removed. However, researchers trying to exploit that ability in hopes of producing artificial liver tissue for transplantation have repeatedly been stymied: Mature liver cells, known as hepatocytes, quickly lose their normal function when removed from the body.

“It’s a paradox because we know liver cells are capable of growing, but somehow we can’t get them to grow” outside the body, said Bhatia. Now, Bhatia and colleagues have taken a step toward that goal. In a paper appearing in the June 2 issue of Nature Chemical Biology, they have identified a dozen chemical compounds that can help liver cells not only maintain their normal function while grown in a lab dish, but also multiply to produce new tissue. Cells grown this way could help researchers develop engineered tissue to treat many of the 500 million people suffering from chronic liver diseases such as hepatitis C, according to the researchers.

Bhatia has previously developed a way to temporarily maintain normal liver-cell function after those cells are removed from the body, by precisely intermingling them with mouse fibroblast cells. The research team adapted the system so that the liver cells could grow, in layers with the fibroblast cells, in small depressions in a lab dish. This allowed the researchers to perform large-scale, rapid studies of how 12,500 different chemicals affect liver-cell growth and function.

In future studies, the MIT team plans to embed the treated liver cells on polymer tissue scaffolds and implant them in mice, to test whether they could be used as replacement liver tissues. They are also pursuing the possibility of developing the compounds as drugs to help regenerate patients’ own liver tissues, working with Trista North and Wolfram Goessling of Harvard Medical School.

Bhatia and colleagues have also recently made progress toward solving another challenge of engineering liver tissue, which is getting the recipient’s body to grow blood vessels to supply the new tissue with oxygen and nutrients. In a paper published in the Proceedings of the National Academy of Sciences in April, Bhatia and Christopher Chen, Professor, University of Pennsylvania, showed that if preformed cords of endothelial cells are embedded into the tissue, they will rapidly grow into arrays of blood vessels after the tissue is implanted.

To achieve this, Kelly Stevens in the Bhatia lab worked with Peter Zandstra, University of Toronto to design a new system that allows them to create 3-D engineered tissue and precisely control the placement of different cell types within the tissue. This approach, described in the journal Nature Communications in May, allows the engineered tissue to function better with the host tissue.

“Together, these papers offer a path forward to solve two of the longstanding challenges in liver tissue engineering - growing a large supply of liver cells outside the body and getting the tissues to graft to the transplant recipient,” said Bhatia.

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