Improved amino acid, bioenergetic metabolite and neurotransmitter profiles following human amnion epithelial cell transplant in intermediate maple syrup urine disease mice.

Abstract

Orthotopic liver transplant (OLT) significantly improves patient outcomes in maple syrup urine disease (MSUD; OMIM: 248600), yet organ shortages point to the need for alternative therapies. Hepatocyte transplantation has shown both clinical and preclinical efficacy as an intervention for metabolic liver diseases, yet the availability of suitable livers for hepatocyte isolation is also limited. Conversely, human amnion epithelial cells (hAEC) may have utility as a hepatocyte substitute, and they share many of the characteristics of pluripotent embryonic stem cells while lacking their safety and ethical concerns. We reported that like hepatocytes, transplantation of hAEC significantly improved survival and lifespan, normalized body weight, and significantly improved branched-chain amino acid (BCAA) levels in sera and brain in a transgenic murine model of intermediate maple syrup urine disease (imsud). In the current report, we detail the neural and peripheral metabolic improvements associated with hAEC transplant in imsud mice, including amino acids associated with bioenergetics, the urea cycle, as well as the neurotransmitter systems for serotonin, dopamine, and gamma-aminobutyric acid (GABA). This stem cell therapy results in significant global correction of the metabolic profile that characterizes the disease, both in the periphery and the central nervous system, the target organ for toxicity in iMSUD. The significant correction of the disease phenotype, coupled with the theoretical benefits of hAEC, particularly their lack of immunogenicity and tumorigenicity, suggests that human amnion epithelial cells deserve serious consideration for clinical application to treat metabolic liver diseases.

• Authors: Kristen J Skvorak, Kenneth Dorko, Fabio Marongiu, Veysel Tahan, Marc C Hansel, Roberto Gramignoli, Erland Arning, Teodoro Bottiglieri, K Michael Gibson, Stephen C Strom
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 109 Issue 2 Pg. 132-8 (Jun 2013) ISSN: 1096-7206 [Electronic] United States
• PMID: 23566440 (Publication Type: Journal Article)
• Copyright: Copyright © 2013. Published by Elsevier Inc.

Chemical References

• Amino Acids
• Neurotransmitter Agents

Topics

• Amino Acids (blood)
• Amnion (cytology)
• Animals
• Brain (metabolism)
• Citric Acid Cycle
• Epithelial Cells (transplantation)
• Humans
• Maple Syrup Urine Disease (blood, therapy)
• Mice
• Mice, Transgenic
• Neurotransmitter Agents (metabolism)