An Intelligent Neural Stem Cell Delivery System for Neurodegenerative Diseases Treatment

Abstract

Transplanted stem cells constitute a new therapeutic strategy for the treatment of neurological disorders. Emerging evidence indicates that a negative microenvironment, particularly one characterized by the acute inflammation/immune response caused by physical injuries or transplanted stem cells, severely impacts the survival of transplanted stem cells. In this study, to avoid the influence of the increased inflammation following physical injuries, an intelligent, double-layer, alginate hydrogel system is designed. This system fosters the matrix metalloproeinases (MMP) secreted by transplanted stem cell reactions with MMP peptide grafted on the inner layer and destroys the structure of the inner hydrogel layer during the inflammatory storm. Meanwhile, the optimum concentration of the arginine-glycine-aspartate (RGD) peptide is also immobilized to the inner hydrogels to obtain more stem cells before arriving to the outer hydrogel layer. It is found that blocking Cripto-1, which promotes embryonic stem cell differentiation to dopamine neurons, also accelerates this process in neural stem cells. More interesting is the fact that neural stem cell differentiation can be conducted in astrocyte-differentiation medium without other treatments. In addition, the system can be adjusted according to the different parameters of transplanted stem cells and can expand on the clinical application of stem cells in the treatment of this neurological disorder.

Multifunctional and Self-Healable Intelligent Hydrogels for Cancer Drug Delivery and Promoting Tissue Regeneration In Vivo

“…The percentage of transplanted survival cells is limited by acute inflammation after injury or transplantation. Therefore, an intelligent double-layer alginate hydrogel system was designed in which an inner layer modified with alginate MMP and RGD polypeptides to improve neural stem cells (NSCs) adhesion, and an outer layer contains Cripto-1 antibodies to facilitate differentiation of NSCs to dopaminergic neurons for treatment of Parkinson’s disease [ 98 ]. In summary, the few covered studies here revealed the feature of injectable self-healable hydrogels to modulate growth, survival, and differentiation of neural cells to target stem cell therapy for the degenerated CNS.…”

Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine

“…However, the xenogeneic nature of ECM‐based scaffolds and the potential immune response to the antigenic components of xenogeneic materials represent a critical barrier to the use of xenogeneic scaffolds in translational applications . Synthetic ECM‐derived peptides, such as laminin‐derived IKVAV and fibronectin‐derived RGD were used to form ECM‐mimetic hydrogels by self‐assembly or incorporation with other biopolymer materials (e.g., hyaluronic acid and alginate) to allow effective delivery and differentiation of stem cells to the brain, without the use of xenogeneic materials.…”

It’s All in the Delivery: Designing Hydrogels for Cell and Non-viral Gene Therapies

“…A double-layered alginate hydrogel system consisting of matrix-metalloproteinases and Arg-Gly-Asp (RGD) peptide in the inner layer was designed to allow transplanted stem cells to proliferate and mobilize to the outer layer following the inflammatory storm caused from surgery. 50 Following transplantation of neural stem cells (NSCs) into a rat brain trauma model, the double-layered alginate hydrogel promoted survival and differentiation of the NSCs. This overall approach focused on NSCs, which have a reduced risk of teratoma formation compared to human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), but the design could be easily adapted to other types of transplanted cells.…”

“…that downregulate gene expression as an effective alternative tool to drive osteogenesis. 50 In addition, the hydrogel's tunable design provides controllable swelling and degradation properties that can be used for prolonged delivery of gene therapies in order to extend the regulation of the transplanted cell behavior.…”