6/24/2011 — Yale New Haven Transplantation Center of Yale-New Haven Hospital has become one of select few centers in the United States and the only center in the Northeast to transplant cryo-preserved liver cells into pediatric patient with metabolic/genetic defect. The procedure, also called a hepatocyte transplant, is beneficial for patients, especially children, with an inherited metabolic disorder called urea cycle defect, in which missing enzymes create toxic products, especially ammonia.
Hepatocyte transplants are being conducted in four other centers in the U.S.; Yale-New Haven is the only hospital in the northeast to offer them. YNHH performed the first pediatric hepatocyte transplant in the country.
Liver cell transplantation is a procedure that shows great promise for the treatment of many diseases now treated only with whole organ transplantation. Organ transplantation involves major surgery, requires the use of scarce donor organs, is expensive and requires life-long immunosuppressive drugs. Potential advantages of cell transplantation include a simpler, safer, less costly procedure that takes advantage of currently discarded liver segments.
Urea-cycle defect is almost always diagnosed neonatal period. In many cases children with urea-cycle defect requires immediate liver transplantation since high blood ammonia level causes major damage in newborns' brain resulting in neurologically severely impaired babies. Since transplanting newborns is very challenging secondary to organ shortage and technical difficulties, hepatocyte transplantation will be a great tool to temporarily control blood ammonia level and prevent development of neurological problems. The hepatocyte transplant will also has some potential immunological benefit if it is done early after birth before newborns immune schooling have not been completed. With some immune manipulations, it could be possible that transplanted hepatocyte will be accepted by babies immune system leading the tolerance induction.
"There is a real need for alternative or supportive techniques in the field of liver transplantation," said Sukru Emre, MD, director, Yale-New Haven Transplantation Center. "Liver cell transplantation is an innovative technique that is especially promising for use in children because it is less invasive than standard liver transplantation."
The liver transplant team, headed by Dr. Emre, performed the first hepatocyte transplantation in a baby with urea-cycle defect in December 2010; the baby was just 21 days old. Led by Dr. Emre,the team infused the healthy liver cells through a catheter into the recipient's portal vein where the new cells travel to the liver, performing the normal liver metabolic functions, including preventing the formation of chemicals detrimental to brain such as ammonia..
"The main objective is to restore full function to the young patient's liver and stop the metabolic crisis," said Dr. Emre. "We also want to stabilize this patient's liver in the hope that rejuvenating the organ even temporarily can bridge the gap so the child becomes a more stable candidate for a liver transplant."
Dr. Emre says that the new liver cells inserted into the native liver of the patient with urea cycle defect could quite possibly begin to perform some of the tasks of a healthy liver within seven to ten days. There is also the distinct possibility that the newly transplanted liver cells could fortify and grow there permanently and slowly regenerate in the organ with pre-existing and healthy working liver cells, postponing or even eliminating the need for a liver transplant.
"Applying these innovative techniques such as hepatocyte transplantation and coupling them with gene therapies in the futures will be the dream work to overcome many metabolic/genetic liver diseases, although we have long way to go" said Dr. Emre.