One Liver for Four Children: First Clinical Series of Liver Cell Transplantation for Severe Neonatal Urea Cycle Defects

Abstract

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.

Hepatocyte transplantation using a living donor reduced graft in a baby with ornithine transcarbamylase deficiency: A novel source of hepatocytes

“…2 HT is less invasive than liver transplantation and can be performed repeatedly. Limitations to the widespread application of HT include the poor availability of hepatocytes.…”

“…On rare occasions, the lack of appropriate donor-recipient matching (eg, infant donor livers) provides good-quality hepatocytes. 2 Fetal livers are also considered to be an alternative cell source, although ethical issues remain to be resolved. At present, we have little choice but to use marginal donor tissues, such as livers obtained from donors after cardiac death and organs with steatosis, fibrosis, or a long ischemia time.…”

Cell Transplantation: A Possible Alternative to Orthotopic Liver Transplant (OLT)

“…Most required OLT at a later date. (Strom et al, 1997a;Horslen et al, 2003;Mitry et al, 2004;Stephenne et al, 2005;Puppi et al, 2008;Meyburg et al, 2009a; …”

“…Single cells succeed in traversing the endothelial barrier and integrate into the parenchyma. After re-establishing intercellular contacts with neighbouring Liver Disease Outcome References α1-antitrypsin (A1AT) No clinical benefit likely due to the presence of fibrosis (Strom et al, 1997a;Strom et al, 1999) Acute liver failure Reversal of disease (Fisher et al, 2000;Soriano, 2002;Fisher & Strom, 2006;Ott et al, 2006) Argininosuccinate lyase deficiency Complete correction (Stephenne et al, 2006) Biliary atresia Partial correction -slow and continuous decrease in bilirubin levels (Khan et al, 2008) Chronic liver failure Bridge to OLT (Bilir et al 200;Strom et al 1997b;Fisher & Strom, 2006;Strom et al, 1999) Citrullinemia Partial correction -decreased citrulline and circulating ammonia at 6 months post-cell infusion (Meyburg et al, 2009a) Crigler-Najjar type 1 Partial correction -slow and continuous decrease in bilirubin levels; evidence of long term correction by hepatocyte graft (one patient was followed for > 1.5 years) (Fox et al, 1998;Ambrosino et al, 2005) Familial cholesterolemia…”

Impact of selected inborn errors of metabolism on prenatal and neonatal development

“…No side effects were observed in our patients. Isolated hepatocyte transplantation in infants with severe urea cycle defects could be a therapeutic option as bridging regimen to overcome the early critical neonatal period (15,16).…”