title: Dopaminergic Induction of Umbilical Cord Mesenchymal Stem Cells by Conditioned Medium of Choroid Plexus Epithelial Cells Reduces Apomorphine-Induced Rotation in Parkinsonian Rats.
abstract: OBJECTIVE
  Degeneration of dopaminergic neurons in Parkinson's disease (PD) implies cell replacement using potentially differentiable sources as a promising therapeutic solution. We tested the capacity of conditioned medium from choroid plexus epithelial cells (CPECs-CM) to induce the dopaminergic potential of umbilical cord matrix mesenchymal stem cells (UCMSCs).
  
  
  METHODS
  We isolated UCMSCs from human umbilical cord and CPECs from rat brain. Following expansion and characterization, CPECs-CM were collected, tested for expression of various growth factors, and applied to UCMSCs. Differentiation was examined and UCMSCs were injected into 6-OHDA-leasioned striatum to test their survival and function.
  
  
  RESULTS
  RT-PCR and immuno-staining demonstrated neuronal/dopaminergic signaling in UCMSCs induced by CPECs-CM and accelerated by addition of retinoic acid (RA) and fibroblast growth factor-2. Expression of β-tubulin-3, Nestin and MAP2 confirmed neuronal differentiation whereas tyrosine hydroxylase, aromatic acid decarboxylase and dopamine transporter were expressed as signs of dopaminergic differentiation. Post-transplantation, the UCMSCs survived, showed reduced rate of apoptosis and led to animals' recovery from apomorphine-induced rotations.
  
  
  CONCLUSIONS
  The combination of neurotrophic factors present in CPECs-CM and RA can synergize to maximize dopaminergic differentiation of potential cell sources including UCMSCs. Our study may have implications for PD cell replacement therapy.
authors.affiliation: 1)National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran. 2)Neuroscience Research Center (NRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3)Anatomy and Cell Biology Department, Shahid Beheshti Uniersity of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Aliaghaei
authors.affiliation: National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Mossa
authors.initials: M
authors.lastname: Gardaneh
authors.affiliation: Neuroscience Research Center (NRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Nader
authors.initials: N
authors.lastname: Maghsoudi
authors.affiliation: Department of Anatomy, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Salehinejad
authors.affiliation: National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Gharib
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000166:cytology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D017077:Culture Media, Conditioned; D018491:Dopamine Agonists; D001058:Apomorphine