title: One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects.
abstract: BACKGROUND
  Urea cycle disorders (UCD) have a poor prognosis despite dietary and pharmacologic therapy, especially if the onset of the disease is within the neonatal period. They are promising target diseases for liver cell transplantation (LCT), which may be a less invasive alternative or supplementation to orthotopic liver transplantation.
  
  
  METHODS
  Cryopreserved hepatocytes were isolated under good manufacturing practice conditions. Four children with severe neonatal UCD (age 1 day-3 years) received multiple intraportal infusions of cryopreserved hepatocytes from that same donor, a 9-day old neonate. Portal vein access was achieved surgically in two children, whereas the umbilical vein was suitable for interventional catheter placement in two neonates. Cell applications were carefully monitored by means of Doppler ultrasound and portal vein pressure.
  
  
  RESULTS
  LCT was feasible in all children. No signs of portal vein thrombosis or extrahepatic shunting were observed. All children showed metabolic stabilization during observation periods of 4 to 13 months. One child with prenatally diagnosed ornithine transcarbamylase deficiency died after 4 months from a fatal metabolic decompensation.
  
  
  CONCLUSIONS
  Given the poor prognosis of UCD with conservative therapy, LCT caused considerable beneficial effects. Periods of hyperammonemia and clinically relevant crises could be reduced during an observation period of up to 13 months. Though cell therapy is not a permanent therapeutic option, bridging to liver transplantation may be substantially improved.
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Heidelberg, Germany. jochen.meyburg@med.uni-heidelberg.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Meyburg
authors.forename: Anibh M
authors.initials: AM
authors.lastname: Das
authors.forename: Friederike
authors.initials: F
authors.lastname: Hoerster
authors.forename: Martin
authors.initials: M
authors.lastname: Lindner
authors.forename: Heinz
authors.initials: H
authors.lastname: Kriegbaum
authors.forename: Guido
authors.initials: G
authors.lastname: Engelmann
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Michael
authors.initials: M
authors.lastname: Ott
authors.forename: Andrea
authors.initials: A
authors.lastname: Pettenazzo
authors.forename: Thomas
authors.initials: T
authors.lastname: Luecke
authors.forename: Harald
authors.initials: H
authors.lastname: Bertram
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.forename: Alberto
authors.initials: A
authors.lastname: Burlina
mesh_terms: D000641:Ammonia / Q000097:blood; D017690:Cell Transplantation / Q000379:methods*; D015925:Cryopreservation; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016031:Liver Transplantation / Q000379:methods*; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000601:surgery*; D011169:Portal Vein / Q000601:surgery; D014019:Tissue Donors; D016896:Treatment Outcome; D014508:Urea / Q000378:metabolism*
chemical_list: D000641:Ammonia; D014508:Urea