title: Placental stem cell correction of murine intermediate maple syrup urine disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Skvorak
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dorko
authors.forename: Fabio
authors.initials: F
authors.lastname: Marongiu
authors.forename: Veysel
authors.initials: V
authors.lastname: Tahan
authors.forename: Marc C
authors.initials: MC
authors.lastname: Hansel
authors.forename: Roberto
authors.initials: R
authors.lastname: Gramignoli
authors.forename: K Michael
authors.initials: KM
authors.lastname: Gibson
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Strom
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000235:genetics / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000235:genetics; D000650:Amnion / Q000166:cytology*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000254:growth & development / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000637:transplantation*; D005260:Female; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D008375:Maple Syrup Urine Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008817:Mice, Mutant Strains; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous
chemical_list: D000597:Amino Acids, Branched-Chain; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)