Permanent expression of midbrain dopaminergic neurons traits in differentiated amniotic epithelial cells.
Amniotic epithelial cells (AECs) have been the subject of interest due to their stem cells characteristics. Pluripotency, lack of teratoma formation, low immunogenicity and no ethical issues make them an alternative source of stem cells for generation of dopaminergic neurons in vitro. AECs may differentiate into midbrain dopaminergic neurons in the presence of induction factors which trigger pathway naturally occurring in the mesencephalon during embryogenesis. In this study, we examined whether FGF8 and Sonic hedgehog (Shh) can induce AECs to express permanently midbrain dopaminergic neurons traits. We found that fresh isolated AECs temporarily expressed some neural markers which decreased 7 days after culture. Co-treatment of cells with FGF8 and Shh had synergistic effect on expression of TH, DAT, Pax2, Lmx1b and En1. Shh ceased differentiation in dopaminergic state and decreased DβH. HPLC analysis revealed that dopamine was released into the medium upon depolarization, indicating that functional dopaminergic neurons were present in the culture. These results demonstrate that AECs have capability to differentiate into dopaminergic neurons and can be a candidate for cell replacement therapy of Parkinson's disease.
Nanomedicine and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. niknejad@sbmu.ac.ir
Hassan
H
Niknejad
Tina
T
Deihim
Abolhassan
A
Ahmadiani
Masoumeh
M
Jorjani
Habibollah
H
Peirovi
D000704:Analysis of Variance; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000494:pharmacology; D053823:Hedgehog Proteins / Q000494:pharmacology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D014157:Transcription Factors / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; C496456:FGF8 protein, human; D053823:Hedgehog Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D051524:Fibroblast Growth Factor 8; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine