title: Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering.
abstract: Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer β-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA(16)-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation.
authors.affiliation: Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Tzu-Yun
authors.initials: TY
authors.lastname: Cheng
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Chen
authors.forename: Wen-Han
authors.initials: WH
authors.lastname: Chang
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Huang
authors.forename: Tzu-Wei
authors.initials: TW
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology* / Q000601:surgery; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018914:Cells, Immobilized / Q000166:cytology / Q000637:transplantation; D002942:Circular Dichroism; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects; D013194:Staining and Labeling; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D010455:Peptides; D049452:Green Fluorescent Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate