Migration and Differentiation of Neural Stem Cells Diverted From the Subventricular Zone by an Injectable Self-Assembling β-Peptide Hydrogel

Abstract

Neural stem cells, which are confined in localised niches are unable to repair large brain lesions because of an inability to migrate long distances and engraft. To overcome these problems, previous research has demonstrated the use of biomaterial implants to redirect increased numbers of endogenous neural stem cell populations. However, the fate of the diverted neural stem cells and their progeny remains unknown. Here we show that neural stem cells originating from the subventricular zone can migrate to the cortex with the aid of a long-lasting injectable hydrogel within a mouse brain. Specifically, large numbers of neuroblasts were diverted to the cortex through a self-assembling β-peptide hydrogel that acted as a tract from the subventricular zone to the cortex of transgenic mice (NestinCreERT2:R26eYFP) in which neuroblasts and their progeny are permanently fluorescently labelled. Moreover, neuroblasts differentiated into neurons and astrocytes 35 days post implantation, and the neuroblast-derived neurons were Syn1 positive suggesting integration into existing neural circuitry. In addition, astrocytes co-localised with neuroblasts along the hydrogel tract, suggesting that they assisted migration and simulated pathways similar to the native rostral migratory stream. Lower levels of astrocytes were found at the boundary of hydrogels with encapsulated brain-derived neurotrophic factor, comparing with hydrogel implants alone.

Staphylococcus aureus entanglement in self-assembling β-peptide nanofibres decorated with vancomycin

“…28 Also, these materials can form biocompatible hydrogels for cell culture [29][30][31][32] and in vivo applications. 33,34 The activity of these b 3 -peptide materials has been modulated through the introduction of novel b-amino acids containing cell adhesion epitopes and uorophores for localisation studies. We therefore aimed to exploit the facile bre formation of b-peptides to prepare an antimicrobial b-peptide bre.…”

The Diverse World of Foldamers: Endless Possibilities of Self-Assembly

“…An extensive effort in the hierarchical self-assembly of β-peptides, directed to the formation of nanofibers that could also form macroscopic fibers, was done by Aguilar’s and Mechler’s groups [ 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ]. In a seminal work, they rapidly obtained both microscopic and macroscopic fibers by simply dissolving various N-terminal acetylated β 3 -tri- and β 3 -hexapeptides in methanol or water, as shown in Figure 6 a.…”

“…According to fluorescence microscopy, SN4741 neuronal progenitor cells deposited on top of the hydrogel showed high cell viability and spreading, but only when serum was added to the culture medium, due to the fact that no cell signaling was incorporated in the β-peptidic scaffold. A long-lasting injectable hydrogel obtained from a 90:10 mixture of C14 Ac-β 3 -tripeptide and an RGD-modified β 3 -tripeptide (Ac-β-hAla(C 14 )-β-hAla(RGD)-β-hLys-OH) in phosphate buffered saline (PBS) was then implanted into transgenic mice [ 130 ], showing by fluorescence microscopy the ability to both divert neural stem cells (NSCs) from the subventricular zone to the cortex and differentiate NCSs into neurons and astrocytes. Interestingly, the experiments also suggested a possible integration of neurons.…”

“… ( a ) The lipidated C14 Ac-β 3 -tripeptide (Refs. [ 123 , 125 , 130 ]) and ( b ) its fluorescent analogue (Ref. [ 129 ]); ( c ) From left to right: schematic representations of fibers formation by 49:1 mixtures of lipidated C14 Ac-β 3 -tripeptide and its fluorescent analogue; confocal image of the corresponding hydrogel showing successful incorporation of the fluorophore into the fiber matrix; in vivo animal imaging 14 days post-injection (ochre cylinders: Ac-β 3 -tripeptide skeleton; zigzag chains: C14 acyl chain; blue spheres: Quasar ® 670 emitting dye) (reprinted with permission from Ref.…”

Injectable Gelatin Hydrogel Suppresses Inflammation and Enhances Functional Recovery in a Mouse Model of Intracerebral Hemorrhage

“…In this regard, hydrogels based on natural proteins, such as collagen and gelatin or decellularized membranes, have the advantage of generally possessing the ligands necessary for cell adhesion. Gelatin derived from denatured and partly degraded collagen, and was widely used in the tissue engineering for its good biodegradability and biocompatibility, as well as adhesion to cells and lack of antigenicity ( Lin et al, 2017 ; Mobaraki et al, 2019 ; Shi et al, 2019a , b ; Zhang et al, 2019 ), and often used for cell encapsulation ( Barthes et al, 2018 ), More importantly, gelatin retains cell adhesive motifs of RGD ( Echave et al, 2017 ), a key biological functional sequence that could be used as an active target ( Ge et al, 2018 ), promote angiogenesis and nerve regeneration ( Li et al, 2017 ; Dursun et al, 2019 ; Samadian et al, 2020 ; Wu et al, 2020 ), reduce gliosis and accelerate neural progenitor cell migration ( Nih et al, 2017 ; Motamed et al, 2019 ), influent inflammation ( Zaveri et al, 2014 ; Nguyen et al, 2016 ), and elicit M2 polarization from macrophages in vitro ( Cha et al, 2017 ; Wang et al, 2018 ; Kang et al, 2019 ) when binds to integrin receptor through ligand-receptor specific interactions. However, in vivo , we know that the interaction between host immunity and the implant depends on the microenvironment of adjacent tissue, resulting in a tissue-specific response to biomaterials ( Taraballi et al, 2018 ; Feng et al, 2019 ; Wang Y. et al, 2019 ).…”