Prenatal Transplantation of Epidermal Neural Crest Stem Cells in Malformation of Cortical Development Mouse Model Publisher Pubmed



Omidi A¹ ; Akbari M¹ ; Mortezaee K² ; Eqlimi E³ ; Beyer C⁴ ; Zendedel A^{4, 5} ; Ragerdi Kashani I¹ Show Affiliations
Source: Microscopy Research and Technique Published:2017

Abstract

Prenatal interventions may offer an immense opportunity in therapeutic protocols of malformations of cortical development (MCD). Epidermal neural crest stem cells (EPI-NCSCs) of the hair follicle bulge exhibit features of both embryonic and adult stem cells; these cells maintain their neurologic differentiation capability because of their neural crest origin. However, it is unknown if prenatal use of EPI-NCSCs could be beneficial in targeting methylazoxymethanol (MAM)-induced MCD, which further addressed in the present work. EPI-NCSCs were prenatally infused to the MAM-exposed mice. Thicknesses of various cerebral cortex areas as well as corpus callosum was measured; there were markedly decrease in MAM group (p <.001 vs. untreated), but a significant increase in EPI-NCSC group (p <.05 vs. MAM), except for corpus callosum. Real-time PCR analysis showed high expressions for absent, small, or homeotic 2-like protein, nestin, doublecortin (DCX), neuronal specific nuclei protein (NeuN), and glial fibrillary acidic protein (GFAP) in MAM group (p <.001 vs. untreated), except for G-protein-coupled C-X-C chemokine receptor type 4 (CXCR4) and CXC motif ligand 12 (CXCL12), whereas there were low expressions in EPI-NCSCs group (p <.01 vs. MAM). Immunohistochemistry of NeuN, GFAP, ionized calcium-binding adapter molecule (Iba1), and oligodendrocyte lineage transcription factor 2 (Olig2) was also revealed the same pattern as real-time PCR (p <.001 MAM vs. untreated, and p <.05 EPI-NCSCs vs. MAM). Our findings suggest prenatal use of EPI-NCSCs as a possible candidate for cell-based therapy of cortical injury through affecting neural markers and their relationship with glial. © 2016 Wiley Periodicals, Inc.