Transplantation of Induced Pluripotent Stem Cells Improves Functional Recovery in Huntington's Disease Rat Model
Author(s) -
Shuhua Mu,
Jiachuan Wang,
Guangqian Zhou,
Wenda Peng,
Zhendan He,
Zhenfu Zhao,
Cuiping Mo,
Junle Qu,
Jian Zhang
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0101185
Subject(s) - quinolinic acid , induced pluripotent stem cell , transplantation , stem cell , striatum , huntington's disease , biology , pathology , microbiology and biotechnology , medicine , neuroscience , embryonic stem cell , dopamine , biochemistry , disease , tryptophan , amino acid , gene
The purpose of this study was to determine the functional recovery of the transplanted induced pluripotent stem cells in a rat model of Huntington's disease with use of 18 F-FDG microPET/CT imaging. Methods In a quinolinic acid-induced rat model of striatal degeneration, induced pluripotent stem cells were transplanted into the ipsilateral lateral ventricle ten days after the quinolinic acid injection. The response to the treatment was evaluated by serial 18 F-FDG PET/CT scans and Morris water maze test. Histological analyses and Western blotting were performed six weeks after stem cell transplantation. Results After induced pluripotent stem cells transplantation, higher 18 F-FDG accumulation in the injured striatum was observed during the 4 to 6-weeks period compared with the quinolinic acid-injected group, suggesting the metabolic recovery of injured striatum. The induced pluripotent stem cells transplantation improved learning and memory function (and striatal atrophy) of the rat in six week in the comparison with the quinolinic acid-treated controls. In addition, immunohistochemical analysis demonstrated that transplanted stem cells survived and migrated into the lesioned area in striatum, and most of the stem cells expressed protein markers of neurons and glial cells. Conclusion Our findings show that induced pluripotent stem cells can survive, differentiate to functional neurons and improve partial striatal function and metabolism after implantation in a rat Huntington's disease model.
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