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Effect of Metformin on Epidermal Neural Crest Stem Cells and Their Potential Application in Ameliorating Paclitaxel-Induced Neurotoxicity Phenotype Publisher Pubmed



Khodabakhsh P1 ; Asgari Taei A2 ; Shafaroodi H3 ; Pournajaf S4 ; Dargahi L5
Authors
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Authors Affiliations
  1. 1. Institute of Physiology, Department Neurophysiology, Eberhard Karls University of Tubingen, Tubingen, Germany
  2. 2. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  5. 5. Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: Stem Cell Reviews and Reports Published:2024


Abstract

Aims: Epidermal Neural Crest Stem Cells (EPI-NCSCs) have emerged as prospective ideal candidates to meet the fundamental requirements of cell-based therapies in neurodegenerative disorders. The present study aimed to identify the potential of metformin in driving EPI-NCSCs to neuronal/glial differentiation and express neurotrophic factors as well as assess their therapeutic potential for mitigating the main behavioral manifestations of chemotherapy-induced neurotoxicity (CIN). Main Methods: EPI-NCSCs were extracted from the bulge region of hair follicle. Following expansion, transcript and protein expression profiles of key markers for stemness (Nestin, EGR-1, SOX-2 and 10), neurotrophic activity (BDNF, GDNF, NGF, FGF-2, and IL-6), and neuronal (TUB3, DCX, NRF and NeuN) and glial (PDGFRα, NG2, GFAP, and MBP) differentiation were determined on days 1 and 7 post-treatment with 10 and 100 μM metformin using real time-PCR and immunocytochemistry methods. Then, the in vivo function of metformin-treated stem cells was evaluated in the context of paclitaxel CIN. To do so, thermal hyperalgesia, mechanical allodynia, and spatial learning and memory tests were evaluated by Hotplate, Von Frey, and Morris water maze tests. Key Findings: Our result indicated that exposure of EPI-NCSCs to metformin was associated with progressive decline in stemness markers and enhanced expression levels of several neurotrophic, neuron and oligodendrocyte-specific markers. Further, it was observed that intranasal metformin-treated EPI-NCSCs improved the cognitive impairment, and mechanical and thermal hypersensitivity induced by paclitaxel in rats. Significance: Collectively, we reasoned that metformin pretreatment of EPI-NCSCs might further enhance their therapeutic benefits against CIN. Graphical Abstract: [Figure not available: see fulltext.]. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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