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Three Institutions Combine Efforts In First-Ever Demonstration Of Long-Term Function In Transplanted Human Liver Cells

Date:
May 15, 1998
Source:
University Of Nebraska Medical Center
Summary:
A team of physicians and scientists from three medical centers has combined forces to show that an infusion of liver cells can function for more than a year to partially correct a patient's rare metabolic liver disease. The procedure, which is reported in this week's New England Journal of Medicine, suggests that cell transplantation may have broader application and be a safer and less invasive treatment than liver transplantation for some patients with disorders of the liver.

A team of physicians and scientists from three medical centers has combined forces to show that an infusion of liver cells can function for more than a year to partially correct a patient's rare metabolic liver disease. The procedure, which is reported in this week's New England Journal of Medicine, suggests that cell transplantation may have broader application and be a safer and less invasive treatment than liver transplantation for some patients with disorders of the liver.

The liver cell infusion took place in April 1997 at the University of Nebraska Medical Center (UNMC) in Omaha and was performed on a 10-year-old girl suffering from Crigler-Najjar Syndrome Type I, a rare disease in which the liver does not make the enzyme that allows bilirubin, a blood cell byproduct, to be normally excreted by the body.

The team performing the procedure was headed by Ira Fox, M.D., a UNMC transplant surgeon who collaborated with J. Roy-Chowdhury, M.D. and N. Roy-Chowdury, Ph.D., liver disease experts at the Albert Einstein College of Medicine in Bronx, N.Y., and Stephen Strom, Ph.D., an expert in isolating human liver cells from the University of Pittsburgh.

"This is an important step forward," Dr. Fox said. "We now know that factors which have limited the long-term effectiveness of pancreatic islet cell transplants for the treatment of diabetes do not affect the long-term function of transplanted liver cells, at least for some liver disorders."

Because the body is unable to conjugate and normally excrete bilirubin, patients with Crigler-Najjar disease develop jaundice and must spend 12 hours a day or longer receiving phototherapy, which helps degrade the bilirubin in the skin, so it can be cleared from the body.

Other than a liver transplant, there is no cure for Crigler-Najjar disease. The oldest living patient with this disease is 31 years old and few people live beyond their teens.

"This is a very insidious disease," Dr. Fox said. "Because of the daily need for phototherapy, patients with this disease can't live a normal life. The light therapy becomes less effective as patients get older, and there is an increasing risk that the high level of bilirubin will cause brain damage, especially if the patient develops an infection."

Because liver transplantation is not without risk, UNMC surgeons decided to try to do the less-invasive cell transplant procedure. The donor liver cells infused into the patient came from a liver that wasn't suitable for whole organ transplantation, but the liver cells were perfectly fine, Dr. Fox said.

The liver cells were isolated from the donor liver by Dr. Strom and his team at the University of Pittsburgh and transported by air carrier to UNMC. From there, the cells were infused through a catheter inserted through the skin just below the patient's breast bone while the patient was awake. The cells traveled through the catheter into a major blood vessel leading into the liver.

Approximately 7 billion cells, comprising about five percent of the liver's total mass, were infused in the course of a 15-hour period. The patient was discharged from the hospital 20 hours after the cell infusion was complete.

Using methods developed by the Roy-Chowdhurys and their colleagues, the team was able to measure the patient's enzyme activity in the liver and analyze the function of the transplanted cells.

Going into the procedure, the patient's bilirubin level was approximately 27 mg/dl. A year after the liver cell transplant, it has been steadily hovering around 12mg/dl. The normal bilirubin level for most people is less than one. However, keeping the patient's bilirubin level below 20mg/dl significantly decreases the risk of brain damage.

Since the procedure, the patient's daily phototherapy has been reduced from 10 to 12 hours per day to between six to seven hours per day, and she has become significantly less jaundiced. Because the donor liver cells are foreign to the patient's body, she must take immunosuppression drugs to prevent her body from rejecting the cells. To date, the authors report no signs of rejection.

She now has two types of cells in her liver, Dr. Strom said. Most are her own cells, which don't produce the enzyme necessary for the excretion of bilirubin, but a portion of the cells are the transplanted cells, which express the enzyme and are able to conjugate bilirubin, thus reducing its levels in the blood.

"Human liver cell transplantation had been tried before, but until now it had not been possible to demonstrate the prolonged survival and function of these cells," Dr. J. Roy-Chowdhury said. "Our studies provide the first unequivocal evidence of the long-term function of transplanted human liver cells."

"Now that we know long-term cell functioning is possible, the infusion of additional liver cells may completely free the patient from the need for phototherapy," Dr. Strom said. "Ultimately, it could mean that this disease, and other diseases of the liver, may be cured without the need for whole-organ transplantation."


Story Source:

The above story is based on materials provided by University Of Nebraska Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Nebraska Medical Center. "Three Institutions Combine Efforts In First-Ever Demonstration Of Long-Term Function In Transplanted Human Liver Cells." ScienceDaily. ScienceDaily, 15 May 1998. <www.sciencedaily.com/releases/1998/05/980515080950.htm>.
University Of Nebraska Medical Center. (1998, May 15). Three Institutions Combine Efforts In First-Ever Demonstration Of Long-Term Function In Transplanted Human Liver Cells. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/1998/05/980515080950.htm
University Of Nebraska Medical Center. "Three Institutions Combine Efforts In First-Ever Demonstration Of Long-Term Function In Transplanted Human Liver Cells." ScienceDaily. www.sciencedaily.com/releases/1998/05/980515080950.htm (accessed July 31, 2014).

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