LONDON (TIP): In a big leap towards creating an artificial human liver, a scientist of Indian origin from Massachusetts Institute of Technology (MIT) has for the first time managed to keep live liver cells functional outside the body. Dr Sangeeta Bhatia, who is presently professor of health sciences and technology has 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.
The liver is the only major organ in the human body that can 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,” says Bhatia, from MIT’s Koch Institute for Integrative Cancer Research.
Dr Bhatia, who originally belongs to a Sindhi family in Mumbai said “The main finding is that we identified chemicals that make liver cells grow outside the body. Cells grown this way can help can incorporated into engineered livers that we are building to treat patients with liver disease. The human liver cells (hepatocytes) can also be used for drug testing to improve drug safety”. “We have showed that human liver cells could be used to build engineered liver tissue and that this liver tissue could function once implanted in the body. So far, we are able to do this in mice.
We need to make them bigger in order to help patients with liver disease.” She added “Tissue engineering has already created artificial skin and cartilage and bone that has helped many millions. Artificial trachea and bladder and blood vessels are also in humans. We will follow the same path that others have laid out for us for the liver”. “The main challenges are to get the liver cells to function like liver cells so they can support the patient, getting enough liver cells for a patient (billions are needed), and ways to implant them so they have enough nutrients through blood vessels (this is called vascularization).
We think we have made good progress on the functional side begins to address the cell sourcing and vascularization issues,” she added. Bhatia has developed a way to temporarily maintain normal livercell function after those cells are removed from the body, by precisely intermingling them with mouse fibroblast cells. They studied how 12,500 different chemicals affect liver-cell growth and function. The liver has about 500 functions, divided into four general categories: drug detoxification, energy metabolism, protein synthesis and bile production.
David Thomas from the Broad Institute, measured expression levels of 83 liver enzymes representing some of the most finicky functions to maintain. After screening thousands of liver cells from eight different tissue donors, the researchers identified 12 compounds that helped the cells maintain those functions, promoted liver cell division, or both. Two of those compounds seemed to work especially well in cells from younger donors. Publishing their breakthrough in the journal Nature Chemical Biology, the team says 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.