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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 Publisher Pubmed



Tavakol S1, 2, 3 ; Saber R1 ; Hoveizi E4 ; Aligholi H5, 6 ; Ai J7, 8 ; Rezayat SM1, 9, 10
Authors
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Authors Affiliations
  1. 1. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469, Iran
  2. 2. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Advanced Medical Sciences and Technologies Association, Student’s Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
  5. 5. Department of Neurosciences, School of Advanced Technologies in medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Shefa Neuroscience Research Center, Khatam al- Anbia Hospital, Tehran, Iran
  7. 7. Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Brain and Spinal Injury Research Center, Imam Hospital, Tehran University of Medical Sciences, Tehran, 1417755469, Iran
  9. 9. Department of Toxicology & Pharmacology, School of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran
  10. 10. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Molecular Neurobiology Published:2016


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. © 2015, Springer Science+Business Media New York.
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