Abstract
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 18F-FDG microPET/CT imaging.MethodsIn 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 18F-FDG PET/CT scans and Morris water maze test. Histological analyses and Western blotting were performed six weeks after stem cell transplantation.ResultsAfter induced pluripotent stem cells transplantation, higher 18F-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.ConclusionOur 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.
Highlights
Huntington’s disease (HD) is characterized by the expansion of CAG repeats in the huntingtin gene and the loss of medium spiny neurons in the striatum, resulting in progressive cognitive impairment, neuropsychiatric symptoms, and involuntary choreiform movements [1]
The aims of the present study were to investigate whether transplanted induced pluripotent stem cells (iPSCs) migrated and survived in quinolinic acid (QA)-injured striatum of rats, improving functional and metabolic deficits of striatum, and whether 18F-FDG PET imaging can monitor the improvement of cerebral energy metabolism in the striatum of rat model of HD
Transplantation of iPSC improves recovery of learning and memory deficits induced by QA
Summary
Huntington’s disease (HD) is characterized by the expansion of CAG repeats in the huntingtin gene and the loss of medium spiny neurons in the striatum, resulting in progressive cognitive impairment, neuropsychiatric symptoms, and involuntary choreiform movements [1]. The neuropathological changes in HD are selective and progressive degeneration of striatal GABAergic medium spiny projection neurons [2]. The transplantation of fetal striatal tissue to the striatum to modify HD progression in humans has been investigated, and some favorable effects have been found [7,8], but it does not alter the toxic effects of mutant huntingtin and has difficulties in tissue availability and viability, high risk of rejection, ethical arguments and concerns about contamination and heterogeneity of the tissues [9]
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