Bioinspired nanofiber scaffold for differentiating bone marrow-derived neural stem cells to oligodendrocyte-like cells: Design, fabrication, and characterization

Boroojeni, F. R ; Sharif University of Technology | 2020

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  1. Type of Document: Article
  2. DOI: 10.2147/IJN.S248509
  3. Publisher: Dove Medical Press Ltd , 2020
  4. Abstract:
  5. Background: Researchers are trying to study the mechanism of neural stem cells (NSCs) differentiation to oligodendrocyte-like cells (OLCs) as well as to enhance the selective differentiation of NSCs to oligodendrocytes. However, the limitation in nerve tissue acces-sibility to isolate the NSCs as well as their differentiation toward oligodendrocytes is still challenging. Purpose: In the present study, a hybrid polycaprolactone (PCL)-gelatin nanofiber scaffold mimicking the native extracellular matrix and axon morphology to direct the differentiation of bone marrow-derived NSCs to OLCs was introduced. Materials and Methods: In order to achieve a sustained release of T3, this factor was encapsulated within chitosan nanoparticles and chitosan-loaded T3 was incorporated within PCL nanofibers. Polyaniline graphene (PAG) nanocomposite was incorporated within gelatin nanofibers to endow the scaffold with conductive properties, which resemble the conductive behavior of axons. Biodegradation, water contact angle measurements, and scanning electron microscopy (SEM) observations as well as conductivity tests were used to evaluate the properties of the prepared scaffold. The concentration of PAG and T3-loaded chitosan NPs in nanofibers were optimized by examining the proliferation of cultured bone marrow-derived mesenchymal stem cells (BMSCs) on the scaffolds. The differentiation of BMSCs-derived NSCs cultured on the fabricated scaffolds into OLCs was analyzed by evaluating the expression of oligodendrocyte markers using immunofluorescence (ICC), RT-PCR and flowcytometric assays. Results: Incorporating 2% PAG proved to have superior cell support and proliferation while guaranteeing electrical conductivity of 10.8 × 10−5 S/cm. Moreover, the scaffold containing 2% of T3-loaded chitosan NPs was considered to be the most biocompatible samples. Result of ICC, RT-PCR and flow cytometry showed high expression of O4, Olig2, platelet-derived growth factor receptor-alpha (PDGFR-α), O1, myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) high expressed but low expression of glial fibrillary acidic protein (GFAP). Conclusion: Considering surface topography, biocompatibility, electrical conductivity and gene expression, the hybrid PCL/gelatin scaffold with the controlled release of T3 may be considered as a promising candidate to be used as an in vitro model to study patient-derived oligodendrocytes by isolating patient’s BMSCs in pathological conditions such as diseases or injuries. Moreover, the resulted oligodendrocytes can be used as a desirable source for transplanting in patients. © 2020 Rasti Boroojeni et al
  6. Keywords:
  7. Central nervous system ; Controlled triiodothyronine release ; Nanofibers scaffold ; Oligodendrocyte cells ; Polyaniline graphene ; Chitosan ; Chitosan nanoparticle ; Glial fibrillary acidic protein ; Graphene ; Molecular scaffold ; Myelin basic protein ; Myelin oligodendrocyte glycoprotein ; Oligodendrocyte transcription factor 2 ; Platelet derived growth factor alpha receptor ; Polyaniline ; Transcription factor ; Transcription factor O1 ; Transcription factor O4 ; Unclassified drug ; Water ; Aniline derivative ; Biomimetic material ; Liothyronine ; Nanofiber ; Polycaprolactone ; Polyester ; Adult ; Animal cell ; Animal tissue ; Article ; Axon ; Biodegradation ; Bone marrow cell ; Bone marrow derived mesenchymal stem cell ; Cell structure ; Contact angle ; Controlled study ; Design ; Extracellular matrix ; Nanoanalysis ; Nanoencapsulation ; Nanofabrication ; Nerve cell differentiation ; Neural stem cell ; Nonhuman ; Protein expression ; Rat ; Stem cell culture ; Animal ; Cell culture ; Chemistry ; Cytology ; Drug effect ; Human ; Mesenchymal stem cell ; Metabolism ; Pig ; Tissue scaffold ; Ultrastructure ; Aniline Compounds ; Animals ; Biomimetic Materials ; Bone Marrow Cells ; Cell Differentiation ; Cell Proliferation ; Cell Shape ; Cell Survival ; Cells, Cultured ; Electric Conductivity ; Gelatin ; Graphite ; Humans ; Mesenchymal Stem Cells ; Nanofibers ; Neural Stem Cells ; Oligodendroglia ; Polyesters ; Rats ; Swine ; Tissue Scaffolds ; Triiodothyronine
  8. Source: International Journal of Nanomedicine ; Volume 15 , 2020 , Pages 3903-3920
  9. URL: https://www.dovepress.com/bioinspired-nanofiber-scaffold-for-differentiating-bone-marrow-derived-peer-reviewed-article-IJN