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Transplantation of Primed or Unprimed Mouse Embryonic Stem Cell-Derived Neural Precursor Cells Improves Cognitive Function in Alzheimerian Rats Publisher Pubmed



Moghadam FH1, 2, 3 ; Alaie H2 ; Karbalaie K1, 4 ; Tanhaei S1, 4 ; Nasr Esfahani MH1, 4 ; Baharvand H4, 5
Authors
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Authors Affiliations
  1. 1. Department of Cell and Molecular Biology, Royan Institute for Animal Biotechnology, Esfahan, P.O. Box 815896-8433, Iran
  2. 2. Department of Physiology, Medical Faculty, Esfahan University of Medical Science, Esfahan, Iran
  3. 3. Department of Physiology, Medical Faculty, Shahid Sadoughi Yazd University of Medical Science, Yazd, Iran
  4. 4. Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, P.O. Box 19395-4644, Iran
  5. 5. Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran

Source: Differentiation Published:2009


Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive and irreversible decline of memory. Neuropathological features include the progressive degeneration of cholinergic neurons in the forebrain cholinergic projection system especially nucleus basalis of Meynert (nbM). New cell therapeutic approaches for the replacement of degenerated cells are being researched. The aim of this study was to investigate the production of cholinergic neurons from mouse embryonic stem cells (ESCs) and potential for utilizing ESC-derived neuronal precursor cells (NPCs) and primed NPCs (PNPCs) for cell restorative therapy in a rodent model of AD. NPCs were produced by growth factor-mediated selection under serum-free conditions and differentiated better into cholinergic neurons when NPCs primed with Shh (~22%) in comparison with different cholinergic promoting factors. Behavioral assessment of unilateral nbM ibotenic acid-lesioned rats by Morris water maze and spatial probe test revealed a significant behavioral improvement in memory deficits following transplantation with NPCs and/or PNPCs. Immunohistochemical analysis revealed that the majority (~70%) of the NPCs and/or PNPCs retained neuronal phenotype and ~40% of them had a cholinergic cell phenotype following transplantation with no tumor formation, indicating that these may be safe for transplantation. This experimental study has important implications as it suggests that the transplantation of mouse ESC-derived NPCs and/or following commitment to a cholinergic cell phenotype can promote behavioral recovery in a rodent model of AD. © 2009 International Society of Differentiation.