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Induced pluripotent stem (iPS) cells for cell replacement therapy in Huntington’s disease (HD)

Choompoo, Narawadee 2015. Induced pluripotent stem (iPS) cells for cell replacement therapy in Huntington’s disease (HD). PhD Thesis, Cardiff University.
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Abstract

Huntington’s disease (HD) is a neurodegenerative disease caused by a mutation in the huntingtin gene (HTT). The extended CAG repeat ultimately leads to loss of medium spiny neurons (MSNs) in the striatum of the HD brain. Cell replacement therapy using primary human fetal tissue as a source of “genuine” MSNs has shown ‘proof of principle’ as a strategy to treat this genetically inherited disease1. However, renewable cell sources need to be identified to overcome the ethical and logistical issues that are associated with using human fetuses. Here we attempted to generate iPS cells by introducing reprogramming factors using the piggyBac Transposon2 transduction system in human fetal fibroblasts and fetal neural stem cells. We wish to test the hypothesis that these cells are more easily reprogrammable and/or are more readily directed towards an MSN phenotype. The established iPS cell lines were similar to human embryonic stem (ES) cells in terms of their morphology, surface antigen, and proliferation. These iPS cells lines have been successfully manipulated to differentiate into MSNs in culture according to their expression of standard molecular markers of premature and mature MSNs - Ctip2 and Darrp32. Differentiation following transplantation into the quinolinic acid (QA) lesion model showed that grafts of these striatal progenitors derived from human fetal iPS cells could differentiate into neural progenitors according to expression of human nuclei marker (HuNu) and nestin.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH426 Genetics
Uncontrolled Keywords: Stem cells, Induced pluripotent stem cells, Neuronal differentiation, Huntington's disease
Funders: Ministry of Science, Thai Royal Goverment
Date of First Compliant Deposit: 30 March 2016
Last Modified: 27 Oct 2017 14:26
URI: http://orca-mwe.cf.ac.uk/id/eprint/73191

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