Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/52259
Title: EFFICIENT DIFFERENTIATION OF FUNCTIONAL DOPAMINERGIC NEURONS FROM HESCS FOR PARKINSON'S DISEASE
Authors: LI MINGMING
Keywords: hESCs, differentiation, dual inhibition, neurogenesis, Parkinson's disease, dopaminergic neurons,
Issue Date: 25-Oct-2013
Source: LI MINGMING (2013-10-25). EFFICIENT DIFFERENTIATION OF FUNCTIONAL DOPAMINERGIC NEURONS FROM HESCS FOR PARKINSON'S DISEASE. ScholarBank@NUS Repository.
Abstract: Parkinson¿s disease (PD) is a severe neurodegenerative disease associated with loss of dopaminergic neurones. Donor fetal tissue transplantation showed promise in addressing some of the symptoms of PD. Derivation of dopaminergic cells from human embryonic stem cells (hESCs) could provide new options for PD therapy. Dopaminergic cells are derived from SOX- floor plate (FP) cells during embryonic development in many species and in human cell culture in vitro. Early treatment with sonic hedgehog (Shh) has been reported to effectively convert hESCs into FP fates. Due to the complex origin of FP cells, we hypothesized a SHH free approach in deriving SOX1- FP cells from hESCs in vitro. Neuroectoderm conversion from hESCs was achieved under dual inhibition of BMP4 (LDN193189) and TGF-ß pathways (SB431542) under minimal condition. Followed by 5 days inhibition with LDN or LDN+SB±PD173074(FGF2 inhibitor), SOX1- FP cells accounts to 70-80% of the whole population. When patterned with SHH and FGF8, the cells were effectively converted to functional Nurr1+ and TH+ dopaminergic cells which accounts for more than 98% of the whole population. However, when the same patterning factors were applied to SOX1+ cells, only less than 4% of the cells are Nurr1+, indicating that patterning only effective when cells exit from SOX1 expression. After transplanting the Nurr1+ and TH+ cells into semi-PD rat model, significant improvement were found in amphetamine induced ipslateral rotations, apomorphine induced contra-lateral rotations and Rota rod motor activates over 8 weeks time.
URI: http://scholarbank.nus.edu.sg/handle/10635/52259
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