Self-Assembling Peptide Nanofiber Containing Long Motif of Laminin Induces Neural Differentiation, Tubulin Polymerization, and Neurogenesis: In Vitro, Ex Vivo, and In Vivo Studies

Abstract

Spinal cord injury (SCI) in humans stayed a ruining and healless disorder. Since longer laminin motif (CQAASIKVAV (CQIK)) better mimics conformation of native region in active site than isoleucine-lysine-valine-alanine-valine (IKVAV) and resulted in improved cellular response so, for the first time in this study, CQIK bounded with two glycines spacer and (RADA)4 as a self-assembling peptide nanofiber backbone (-CQIK) was used. The purpose of this study was to investigate the role of -CQIK in neural differentiation of human endometrial-derived stromal cells (hEnSCs) in vitro, tubulin polymerization ex vivo, and assess the supportive effect of this hydrogel in an animal model of chronic SCI. Results disclosed that proton concentration has direct effect on hEnSCs membrane damage but not on neuroblastoma cells. However, cell viability of neuroblastoma encapsulated into -CQIK was higher than hEnSCs at the concentration of 0.125 % v/w. Gene expression data confirmed neurogenesis, TH over-expression, and glial fibrillary acidic protein (GFAP) suppression eventually through α6 and β1 integrin site. However, it revealed higher neurogenesis as compared to bone morrow homing peptides (BMHP). Although, Basso, Beattie, Bresnahan (BBB) score of chronic model of SCI in rat was higher than control and phosphate-buffered saline (PBS) group but significantly was less than BMHP group. However, -CQIK had induced neurite outgrowth and myelination and inhibited astrogliosis. Tubulin polymerization data using UV spectroscopy showed higher degree of polymerization. However, tubulin polymerization was dependent on nanofiber concentration. Based on our results, it might be concluded that peptidic nanofiber containing long motif of laminin holds great promise for spinal cord injury recovery with increment of neurogenesis and astrogliosis decrement.

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

“…[ 89 ] Furthermore, a longer laminin motif (CQAASIKVAV (CQIK)) bound with two glycine spacer is tethered to RADA16‐I peptide to support neural differentiation of human endometrial‐derived stromal cells and motor neuron recovery in spinal cord injury. [ 90 ] Owing to the peptide backbone design, despite the bioactive motif decoration, RADA16‐I peptide hydrogels yet have predominant β‐sheet structure and form the nanofibrous entangled networks in hydrogel. Two longer functional motifs PRGDSGYRGDS and KLTWQELYQLKYKGI bound to RADA16‐I peptide still do not change nanofibrous networks of RADA16‐I peptide in hydrogel and contrarily form a uniform and interwoven long nanofiber architecture with extrusion of functional motifs from the nanofiber surface, [ 91 ] which not only provide the more optimal bioengineering cell microenvironments for endothelial cell migration and sprouting in vitro, but extensively promote the vessel lumen formation.…”

A Cell-Free SDKP-Conjugated Self-Assembling Peptide Hydrogel Sufficient for Improvement of Myocardial Infarction

“…To prepare the hydrogel, we mixed the (RADA)4-SDKP solution with an equal volume of phosphate-buffered saline (PBS) to form the gel with a final concentration of 0.25% after 1 min. The 0.25% concentration of SAP hydrogel has been used before [40] and proposed by in vivo protocols of PuraMatrix TM , which is composed of (RADA)4 hydrogel.…”

Therapeutic effects of kaempferol affecting autophagy and endoplasmic reticulum stress

“…Overall, based on the morphology, appearance and downstream signal transduction triggered following internal and external stimulation in damaged cells, there are multiple distinct types of cell death, for example, apoptosis (Type I cell death) (Asl et al, ), autophagy (Type II cell death), and necrosis (Type III cell death). Noteworthy, clarifying the exact mechanisms and signaling pathways thereof of interest and finding out the impacts of the certain drugs on RCD would be promising to develop special pharmaceutics in the treatment of neurodegenerative disorders (Tavakol et al, , , ), cancer (Tavakol, ), and so on. The aim of this review is to discuss the association of kaempferol (as a natural compound) with autophagy and endoplasmic reticulum (ER) stress mechanisms.…”