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Generating cholangiocytes to study and treat liver disorders

Post-Doctoral Education Grant Recipient: Nidhi Jalan-Sakrikar, PhD

Faculty Sponsor: Robert C. Huebert

Grant Period: 2015-2016

Site: Mayo Clinic

Click here to read Jalan-Sakrikar's Final Report

Cholangiocytes are the specialized cells that line the bile ducts within the liver. These cells are the target of a group of liver diseases, known as cholangiopathies, which currently can’t be treated without completing a liver transplant. Liver transplants are not widely available, and even when a match is found, the surgery is risky, and the patient's body may refuse the transplanted liver.

Researchers realize that the best option would be to develop alternate therapies for treating cholangiopathies that could directly repair the diseased cholangiocytes. So far, though, researchers have been unsuccessful in developing proven treatments, and even advances made in the laboratory may not be effective when applied to the patient.

The lab completing this research project has pioneered a new method for generating cholangiocytes from stem cells. The stem cells are produced from the patients’ own skin cells, providing a minimally-invasive method to study and potentially treat liver disorders.

In this particular study, the researchers will use stem cells derived from the skin cells of patients who have primary sclerosing cholangitis (PSC), which is a liver disorder that attacks the cholangiocytes. The researcher will differentiate the stem cells into cholangiocytes, which will allow her to study the mechanisms by which liver stem cells differentiate into cholangiocytes in patients with the liver disorder. It is a minimally invasive procedure, yet it allows scientists to closely watch what is happening in individuals with PSC.

This study will enhance the understanding of liver disease in the medical community, whereby opening up new avenues to help treat patients with PSC. The cholangiocytes in the lab will be available for researchers to test potential therapeutic approaches under laboratory conditions. If successful, these therapies could be applied to cells to then be transplanted back into patients as a potential way of treating the disease without having to undergo a liver transplant.

This research will advance the field of regenerative medicine, as scientists will learn valuable information about how specific liver diseases function and what types of therapies might be able to treat the diseases without liver transplants. If the research is successful, and new methods of liver therapy are discovered, the results could save the lives of thousands of individuals who are suffering from liver diseases such as PSC.