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Self-Assembling Peptide Nanofiber Containing Long Motif of Laminin Induces Neural Differentiation, Tubulin Polymerization, and Neurogenesis: In Vitro, Ex Vivo, and In Vivo Studies

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Abstract

Spinal cord injury (SCI) in humans stayed a ruining and healless disorder. Since longer laminin motif (CQAASIKVAV (CQIK)) better mimics conformation of native region in active site than isoleucine-lysine-valine-alanine-valine (IKVAV) and resulted in improved cellular response so, for the first time in this study, CQIK bounded with two glycines spacer and (RADA)4 as a self-assembling peptide nanofiber backbone (-CQIK) was used. The purpose of this study was to investigate the role of -CQIK in neural differentiation of human endometrial-derived stromal cells (hEnSCs) in vitro, tubulin polymerization ex vivo, and assess the supportive effect of this hydrogel in an animal model of chronic SCI. Results disclosed that proton concentration has direct effect on hEnSCs membrane damage but not on neuroblastoma cells. However, cell viability of neuroblastoma encapsulated into -CQIK was higher than hEnSCs at the concentration of 0.125 % v/w. Gene expression data confirmed neurogenesis, TH over-expression, and glial fibrillary acidic protein (GFAP) suppression eventually through α6 and β1 integrin site. However, it revealed higher neurogenesis as compared to bone morrow homing peptides (BMHP). Although, Basso, Beattie, Bresnahan (BBB) score of chronic model of SCI in rat was higher than control and phosphate-buffered saline (PBS) group but significantly was less than BMHP group. However, -CQIK had induced neurite outgrowth and myelination and inhibited astrogliosis. Tubulin polymerization data using UV spectroscopy showed higher degree of polymerization. However, tubulin polymerization was dependent on nanofiber concentration. Based on our results, it might be concluded that peptidic nanofiber containing long motif of laminin holds great promise for spinal cord injury recovery with increment of neurogenesis and astrogliosis decrement.

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Acknowledgments

This work was supported by grant from Iran National Science Foundation (INSF) for the financial support (grant number 92022532) and Tehran University of Medical Sciences, (TUMS) Tehran, Iran Grant Number (93-01-87-23996).

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Authors and Affiliations

  1. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469, Iran

    Shima Tavakol, Reza Saber & Seyed Mahdi Rezayat

  2. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran

    Shima Tavakol

  3. Advanced Medical Sciences and Technologies Association, Student’s Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Shima Tavakol

  4. Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

    Elham Hoveizi

  5. School of Medicine, Kashan University of Medical Sciences, Kashan, Iran

    Behnaz Tavakol

  6. Department of Neurosciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Hadi Aligholi

  7. Shefa Neuroscience Research Center, Khatam al- Anbia Hospital, Tehran, Iran

    Hadi Aligholi

  8. Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Jafar Ai

  9. Brain and Spinal Injury Research Center, Imam Hospital, Tehran University of Medical Sciences, Tehran, 1417755469, Iran

    Jafar Ai

  10. Department of Toxicology and Pharmacology, School of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran

    Seyed Mahdi Rezayat

  11. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mahdi Rezayat

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  1. Shima Tavakol
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  2. Reza Saber
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  4. Behnaz Tavakol
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Correspondence to Jafar Ai or Seyed Mahdi Rezayat.

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Tavakol, S., Saber, R., Hoveizi, E. et al. Self-Assembling Peptide Nanofiber Containing Long Motif of Laminin Induces Neural Differentiation, Tubulin Polymerization, and Neurogenesis: In Vitro, Ex Vivo, and In Vivo Studies. Mol Neurobiol 53, 5288–5299 (2016). https://doi.org/10.1007/s12035-015-9448-z

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  • DOI: https://doi.org/10.1007/s12035-015-9448-z

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