title: Mechano-Transduction Signals Derived from Self-Assembling Peptide Nanofibers Containing Long Motif of Laminin Influence Neurogenesis in In-Vitro and In-Vivo.
abstract: Astroglial scaring and limited neurogenesis are two problematic issues in recovery of spinal cord injury (SCI). In the meantime, it seems that mechanical manipulations of scaffold to inhibit astroglial scarring and improve neurogenesis is worthy of value. In the present investigation, the effect of nanofiber (gel) concentration as a mechanical-stimuli in neurogenesis was investigated. Cell viability, membrane damage, and neural differentiation derived from endometrial stem cells encapsulated into self-assembling peptide nanofiber containing long motif of laminin were assessed. Then, two of their concentrations that had no significant difference of neural differentiation potential were selected for motor neuron investigation in SCI model of rat. MTT assay data showed that nanofibers at the concentrations of 0.125 and 0.25 % w/v induced higher and less cell viability than others, respectively, while cell viability derived from higher concentrations of 0.25 % w/v had ascending trend. Gene expression results showed that noggin along with laminin motif over-expressed TH gene and the absence of noggin or laminin motif did not in all concentrations. Bcl2over-expression is concomitant with the decrease of nanofiber stiffness, NF+cells increment, and astrogenesis inhibition and dark neuron decrement in SCI model. It seems that stiffness affects on Bcl2gene expression and may through β-Catenin/Wnt signaling pathway and BMP-4 inhibition decreases astrogenesis and improves neurogenesis. However, stiffness had a significant effect on upregulation of GFAP+cells and motor neuron recovery in in vivo. It might be concluded that eventually there is a critical definitive point concentration that at less or higher than of it changes cell behavior and neural differentiation through different molecular pathways.
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469, Iran. shima.tavakol@yahoo.com.|Drug Nanocarriers Research Core, Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran. shima.tavakol@yahoo.com.|Student's Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran. shima.tavakol@yahoo.com.
authors.forename: Shima
authors.initials: S
authors.lastname: Tavakol
authors.affiliation: Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
authors.forename: Sayed Mostafa Modarres
authors.initials: SMM
authors.lastname: Mousavi
authors.affiliation: School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Tavakol
authors.affiliation: Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Hoveizi
authors.affiliation: Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Jafar_ai@tums.ac.ir.|Brain and Spinal Injury Research Center, Imam Hospital, Tehran University of Medical Sciences, Tehran, 1417755469, Iran. Jafar_ai@tums.ac.ir.
authors.forename: Jafar
authors.initials: J
authors.lastname: Ai
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469, Iran. rezayat@tums.ac.ir.|Department of Toxicology and Pharmacology, School of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran. rezayat@tums.ac.ir.|Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. rezayat@tums.ac.ir.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezayat@tums.ac.ir.
authors.forename: Seyed Mahdi Rezayat
authors.initials: SMR
authors.lastname: Sorkhabadi
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001713:Biphenyl Compounds / Q000737:chemistry; D002466:Cell Nucleolus / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004717:Endometrium / Q000166:cytology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007382:Intermediate Filaments / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007797:Laminin / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D057139:Nanofibers / Q000737:chemistry*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D010851:Picrates / Q000737:chemistry; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D001713:Biphenyl Compounds; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D010455:Peptides; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl; D007770:L-Lactate Dehydrogenase
keywords: Laminin; Mechano-transduction; Nanofiber; Neurogensis; Self assembling pepetide