title: Enhancement of polysialic acid expression improves function of embryonic stem-derived dopamine neuron grafts in Parkinsonian mice.
abstract: There has been considerable progress in obtaining engraftable embryonic stem (ES) cell-derived midbrain dopamine neurons for cell replacement therapy in models of Parkinson's disease; however, limited integration and striatal reinnervation of ES-derived grafts remain a major challenge for future clinical translation. In this paper, we show that enhanced expression of polysialic acid results in improved graft efficiency in correcting behavioral deficits in Parkinsonian mice. This result is accompanied by two potentially relevant cellular changes: greater survival of transplanted ES-derived dopamine neurons and robust sprouting of tyrosine hydroxylase-positive processes into host tissue. Because the procedures used to enhance polysialic acid are easily translated to other cell types and species, this approach may represent a general strategy to improve graft integration in cell-based therapies.
authors: Center for Stem Cell Biology, Developmental Biology Program, and Cell Biology Program, Sloan-Kettering Institute for Cancer Research, New York, New York, USA.
authors: Daniela
authors: D
authors: Battista
authors: Yosif
authors: Y
authors: Ganat
authors: Abderrahman
authors: A
authors: El Maarouf
authors: Lorenz
authors: L
authors: Studer
authors: Urs
authors: U
authors: Rutishauser
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology*; D053595:Embryonic Stem Cells / Q000166:cytology*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D016501:Neurites / Q000502:physiology; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010641:Phenotype; D012794:Sialic Acids / Q000096:biosynthesis* / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism
chemical_list: D012794:Sialic Acids; C021319:polysialic acid; D012799:Sialyltransferases; D004298:Dopamine
keywords: Brain tissue transplantation; Dopaminergic neurons; Embryonic stem cells; Neuronal plasticity; Parkinson disease; Sialic acids