Abstract
Scaffold materials, neurotrophic factors, and seed cells are three elements of neural tissue engineering. As well-known self-assembling peptide-based hydrogels, RADA16-I and modified peptides are attractive matrices for neural tissue engineering. In addition to its neuroprotective effects, cerebral dopamine neurotrophic factor (CDNF) has been reported to promote the proliferation, migration, and differentiation of neural stem cells (NSCs). However, the role of RADA16-I combined with CDNF on NSCs remains unknown. First, the effect of RADA16-I hydrogel and CDNF on the proliferation and differentiation of cultured NSCs was investigated. Next, RADA16-I hydrogel and CDNF were microinjected into the lateral ventricle (LV) of middle cerebral artery occlusion (MCAO) rats to activate endogenous NSCs. CDNF promoted the proliferation of NSCs, while RADA16-I induced the neural differentiation of NSCs in vitro. Importantly, both RADA16-I and CDNF promoted the proliferation, migration, and differentiation of endogenous NSCs by activating the ERK1/2 and STAT3 pathways, and CDNF exerted an obvious neuroprotective effect on brain ischemia-reperfusion injury. These findings provide new information regarding the application of the scaffold material RADA16-I hydrogel and the neurotrophic factor CDNF in neural tissue engineering and suggest that RADA16-I hydrogel and CDNF microinjection may represent a novel therapeutic strategy for the treatment of stroke.
Highlights
The results demonstrated that cerebral dopamine neurotrophic factor (CDNF) promoted the proliferation of neural stem cells (NSCs) and that RADA16-I
The in vivo data demonstrated that both RADA16-I and CDNF promoted the proliferation of NSCs and neuroblasts in the subventricular zone (SVZ) and the migration of neuroblasts to the ischemic penumbra by activating the ERK1/2 and STAT3 pathways
The results showed that expression levels of phosphorylated ERK1/2 (p-ERK1/2) were significantly increased in the RADA16-I + CDNF group compared to the other groups (F (3, 8) = 16.614; p < 0.001, post hoc p < 0.001, Figure 6A), and expression levels of Ser727 phosphorylated STAT3 (p-STAT3) were significantly elevated in the CDNF treatment groups compared to the control group (F (3, 12) = 5.233; p = 0.015, post hoc p = 0.016, Figure 6B)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The effects of the RADA16-I hydrogel and its modification with laminin have been investigated using human NPCs. The modified peptide induced cell differentiation with the highest dopaminergic maturation of neurons [5]. Cell survival was enhanced [9] Given these findings, RADA16-I and modified peptides are attractive matrices for neural tissue engineering. The in vivo data demonstrated that both RADA16-I and CDNF promoted the proliferation of NSCs and neuroblasts in the SVZ and the migration of neuroblasts to the ischemic penumbra by activating the ERK1/2 and STAT3 pathways. Compared to RADA16-I, CDNF exerted a significant neuroprotective effect on brain ischemia-reperfusion injury This finding indicates the possibility of activating endogenous NSCs for brain injury repair using.
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