title: Chimeric Self-assembling Nanofiber Containing Bone Marrow Homing Peptide's Motif Induces Motor Neuron Recovery in Animal Model of Chronic Spinal Cord Injury; an In Vitro and In Vivo Investigation.
abstract: To date, spinal cord injury (SCI) has remained an incurable disaster. The use of self-assembling peptide nanofiber containing bioactive motifs such as bone marrow homing peptide (BMHP1) as an injectable scaffold in spinal cord regeneration has been suggested. Human endometrial-derived stromal cells (hEnSCs) have been approved by the FDA for clinical application. In this regard, we were interested in investigating the role of BMHP1 in hEnSCs' neural differentiation in vitro and evaluating the supportive effects of this scaffold in rat model of chronic SCI. 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), lactate dehydrogenase (LDH) release, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay, real-time PCR, and immunocyotochemistry (ICC) were performed as a biocompatibility and neural differentiation evaluations on neuron-like hEnSC-derived cells encapsulated into nanofiber. Nanofiber was implanted into rats and followed by behavioral test, Nissl, luxol fast blue (LFB) staining and immunohistostaining (IHC). Results indicated that cell membrane of neuroblastoma cells were more sensitive than hEnSCs to concentration of proton and cell proliferation decreased with increase of concentration. This effect might be related to oxygen tension and elastic modules of scaffold. -BMHP1 nanofiber induced neural differentiation in hEnSC and decreased GFAP gene and protein as a marker of reactive astrocytes in vitro and in vivo. A reason for this finding might be related to the role of spacer number in induction of mechano-transduction signals. The presented study revealed the chimeric BMHP1 nanofiber induced higher axon regeneration and myelniation around the cavity and motor neuron function was encouraged to improve with less inflammatory response following SCI in rats. These effects were possibly due to nanostructured topography and mechano-transduction signals derived from hydrogel at low concentration.
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469, Iran.|Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.|Advanced Medical Sciences and Technologies Association, Student's Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shima
authors.initials: S
authors.lastname: Tavakol
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Saber
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 Neurosciences, School of Advanced Technologies in medicine, Tehran University of Medical Sciences, Tehran, Iran.|Shefa Neuroscience Research Center, Khatam al- Anbia Hospital, Tehran, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Aligholi
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@sina.tums.ac.ir.|Department of Toxicology & Pharmacology, School of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran. rezayat@sina.tums.ac.ir.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezayat@sina.tums.ac.ir.
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Rezayat
mesh_terms: D000217:Acyltransferases / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D020816:Amino Acid Motifs; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001713:Biphenyl Compounds / Q000737:chemistry; D001812:Blood-Brain Barrier / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D002908:Chronic Disease; D004195:Disease Models, Animal; D004717:Endometrium / Q000166:cytology; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology*; D057139:Nanofibers / Q000737:chemistry*; D010851:Picrates / Q000737:chemistry; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D000217:Acyltransferases; D015415:Biomarkers; D001713:Biphenyl Compounds; D007770:L-Lactate Dehydrogenase; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl; C581357:Mboat7 protein, mouse
keywords: BMHP1; Motor neuron function; Neural differentiation; Self-assembling peptide nanofiber