title: Acute course of deferoxamine promoted neuronal differentiation of neural progenitor cells through suppression of Wnt/β-catenin pathway: a novel efficient protocol for neuronal differentiation.
abstract: Neural progenitor cells (NPCs) are feasible therapeutically model cells in regenerative medicine. However, a number of obstacles oppose their applications including insufficiency in differentiation protocols. These complications should be overwhelmed to obtain a significant clinical application. Deferoxamine (DFO), as a small molecule with a clinically high-affinity to chelate intracellular Iron, has been granted orphan drug status for treatment of traumatic spinal cord injury, while its neuroprotective function is not well understood. The aim of the present study is evaluating whether DFO could modulate neuronal differentiation process of NPCs. A varies concentrations of DFO were used to promote neuronal differentiation of mouse and human NPCs with different serum condition as an extracellular source of Iron. Several neural markers were assessed by RT-qPCR and Western analysis. Meanwhile β-catenin content was evaluated as key member of Wnt pathway. The maximal neuronal differentiation rate was observed when treating cells were treated with acute dosage of DFO (100 μM) for 6h in serum free condition. This treatment produced a significant increase in expression of neuronal markers and resulted in dramatically decrease in expression of glial markers. The protein content of β-catenin was also decreased by this treatment. Despite of chronic concentration of DFO, which reduced the size of EBs apparently due to G1/S arrest of cell cycle as known features of DFO. Application of acute courses of DFO increased neuronal differentiation rate of NPCs in serum free conditions. We concluded that suppression of Wnt/β-catenin pathway was induced through chelating of intracellular Iron due to DFO treatment. These findings help to understand therapeutic benefit of DFO as a neuroprotective agent.
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors: Amin
authors: A
authors: Ziaei
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors: Mohammad Reza Piri
authors: MR
authors: Ardakani
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors: Motahare-Sadat
authors: MS
authors: Hashemi
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors: Maryam
authors: M
authors: Peymani
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran; Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran. Electronic address: kamranghaedi@royaninstitute.org.
authors: Kamran
authors: K
authors: Ghaedi
authors: Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
authors: Hossein
authors: H
authors: Baharvand
authors: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address: mh_nasr@royaninstitute.org.
authors: Mohammad Hossein
authors: MH
authors: Nasr-Esfahani
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D003676:Deferoxamine
keywords: Deferoxamine; Iron; Neural progenitor cell; Neuronal differentiation; β-catenin