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center : Isfahan University of Medical Sciences
Document Type : Latin Dissertation
Language of Document : English
Record Number : 102702
Doc. No : T11288
Call number : ‭QU,328,H763e,2008‬
Main Entry : HomayouniMoghadam, Farshad
Title & Author : Evelaution of factors that induce differentiation of mouse embryonic stem cells to cholinergic neurons. Farshad HomayouniMoghadam/فرشاد همایونی‌مقدم
College : Schools, Medical
Date : , 2008
Degree : Physiology, Ph.D
Page No : 88 p.: ill( som col ), diag, tab
Note : This thesis is also a research project with project ID 384257
Note : Orginal Works
Abstract : Introduction: Pluripotent embryonic stem cells (ESCs) can give rise to neuroectodermal derivatives in culture. This potential could be harnessed to generate neurons and glia for cell-replacement therapies in the brain and spinal cord neurodegenerative diseases. Aim:The aim of this study was to evaluate the effect of sonic hedgehog peptide (Shh), retinoic acid (RA), leukemia inhibitory factor (LIF), interleukin-6 (IL6), and nerve growth factor (NGF) on differentiation of neural progenitor cells (NPCs) derived from mouse ESCs to cholinergic neurons. Also these produced neural cells were transplanted in brain of NBM (Nucleus Basalis Magnocellularis) lesioned rats and the differentiation potential and therapeutic effects of grafted cells in improvement of spatial memory function were investigated. Material and methods: Royan B1, mouse ESCs was used to produce neural progenitor cells (NPCs), NPCs were further cultured in presence or absence of differentiation factors. These cells were then prepared for transplantation or cultured for another .7 days in Neurobasal medium to generate neurons. Relative number of neurons and cholinergic neurons were revealed by immunocytochemical staining procedures. RTPCR analyses were also performed to evaluate the expression of specific neuronal markers. Bromodeoxyuridine (Brdu) labeled neural cells and ES cells were grafted after unilateral Nucleus Basalis Magnocellularis (NBM) lesioning in male Wistar rats. Morris water maze (MWM) test were performed in neural cell grafted rats. After memory tests the brain of rats were fixed, sectioned, and then stained by immunofluoroscent techniques. Results: Data show that around 70 of cells were neurons. The percentage of cholinergic neurons was significantly P<0.05 greater in RA and Shh and LIF treated cultures than non treated groups. Our data from grafts indicated that transplanted cells were differentiated to neurons and glial cells and also cholinergic neurons. Morris water maze tests showed the significant difference in neural cell grafted groups compares with lesioned and ES cell transplanted groups. Conclusion: This study Indicated that percentage of cholinergic neurons derived from ESCs increased after treatment by Shh, LIF and RA. These cells could be transplanted and differentiated in vivo to neural cells. Behavioral studies revealed that the transplanted cells integrated as cholinergic neurons and attenuated Ibotenic acid-induced neurological symptoms. Key words: Stem cell, Neuron, Cholinergic, Differentiation, Transplantation.
Descriptor : 1. Cell Physiology.- Descriptors: Embryonic Stem Cells
: Cell Differentiation
: Cell Culture
: Transplantation
: Fetus
: Central Nervous System
Added Entry : Alaie, Hojatollah, Supervisor
: Nasr Esfahani, Mohammad, Supervisor
: Baharvand, Hossein, Supervisor
Translated Title Supplied by Cataloguer : بررسی اثر عوامل کولینرژیک کننده( ‭Sonic Hedghog Peptide ( Shh‬ رتینوئیک اسید ‭RA‬ فاکتور مهار لوسمی ‭LIF‬ اینترلوکین‭۶ ‬-( ‭( IL6‬ و فاکتور رشد عصب ‭NGF‬ بر تمایز سلولهای پیش ساز عصبی ‭NPC‬
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