Potential conflict of interest: Stephen C. Strom holds stock in Stemnion, LLC.
Steatohepatitis/Metabolic Liver Disease
Article first published online: 15 FEB 2013
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 57, Issue 3, pages 1017–1023, March 2013
How to Cite
Skvorak, K. J., Dorko, K., Marongiu, F., Tahan, V., Hansel, M. C., Gramignoli, R., Gibson, K. M. and Strom, S. C. (2013), Placental stem cell correction of murine intermediate maple syrup urine disease. Hepatology, 57: 1017–1023. doi: 10.1002/hep.26150
Supported in part by the National Institutes of Health (Grants N01-DK-7-0004/HHSN26700700004C and RC1DK086135 to S. C. S.) and the National PKU Alliance (R. G. and K. J. S. and Grant HD58553 to K. M. G.).
- Issue published online: 28 FEB 2013
- Article first published online: 15 FEB 2013
- Accepted manuscript online: 23 NOV 2012 12:00AM EST
- Manuscript Accepted: 15 OCT 2012
- Manuscript Received: 20 MAR 2012
There is improved survival and partial metabolic correction of a mouse intermediate maple syrup urine disease (iMSUD) model after allogenic hepatocyte transplantation, confirming that a small number of enzyme-proficient liver-engrafted cells can improve phenotype. However, clinical shortages of suitable livers for hepatocyte isolation indicate a need for alternative cell sources. Human amnion epithelial cells (hAECs) share stem cell characteristics without the latter's safety and ethical concerns and differentiate to hepatocyte-like cells. Eight direct hepatic hAEC transplantations were performed in iMSUD mice over the first 35 days beginning at birth; animals were provided a normal protein diet and sacrificed at 35 and 100 days. Treatment at the neonatal stage is clinically relevant for MSUD and may offer a donor cell engraftment advantage. Survival was significantly extended and body weight was normalized in iMSUD mice receiving hAEC transplantations compared with untreated iMSUD mice, which were severely cachectic and died ≤28 days after birth. Branched chain α-keto acid dehydrogenase enzyme activity was significantly increased in transplanted livers. The branched chain amino acids leucine, isoleucine, valine, and alloisoleucine were significantly improved in serum and brain, as were other large neutral amino acids. Conclusion: Placental-derived stem cell transplantation lengthened survival and corrected many amino acid imbalances in a mouse model of iMSUD. This highlights the potential for their use as a viable alternative clinical therapy for MSUD and other liver-based metabolic diseases. (HEPATOLOGY 2013)