Study On Regulation Of Neural Stem Cells By Materials

The regeneration of central nervous system (CNS) is world wide puzzle, and tissue engineering is one of promising strategies to promote the regeneration of CNS. Neural stem cells could self-renew and differentiate into neurons and glial cells and are an ideal cell source for CNS tissue engineering to treat degenerative diseases and injury in CNS. The study on regulation of neural stem cells by biomaterials and potential use of biomaterials in combination with neural stem cell is very important for CNS tissue engineering.The surfaces modified with different chemical groups, including hydroxyl, sulfonic, amine, carboxyl, mercapto and methyl groups were firstly used to regulate the behaviors of neural stem cells. It can be concluded that surface chemical groups exhibited effects on the regulation of neural stem cells, such as cell adhesion, migration and differentiation of neural stem cells, even the communication between neurospheres. Therefore, the factors responsible for the interactions between cultured neural stem cells and biomaterials should be defined in molecular terms of chemical groups.The study on the behaviors of neural stem cells in the hyaluronic acid/polylysine (HA/PLL) hydrogels was performed. After culture for 5 days, neural stem cells at the level of single cell, survived and differentiated into neurons and astrocytes, while neurosphere-forming cells migrated from their original aggregate and maintained the phonotype of neural stem cells. These studies, carried out in the absence of serum, proved that HA/PLL hydrogels provided a good microenvironment for neural stem cells.A new scaffold material for CNS tissue engineering has been developed by covalently attaching IgG anti-NgR to HA/PLL hydrogels via the hydrolytically unstable hydrazone linkage. This composite HA/PLL/anti-NgR hydrogel had highly porous structure, bio-degradability and similar viscoelastic properties to neural tissue. Furthermore, after implantation into the injured brain of rat model, the polymer hydrogel could correctly bridge the tissue defects, inhibit the formation of glial scar and form a permissive interface with the host tissue to favour neural cell ingrowth.Neural stem cells were seeded into HA/PLL/anti-NgR hydrogels, and this composite hydrogel exhibited a good micro-environment for differentiation of neural stem cells and maturation of differentiating neurons. The in vivo study of HA/PLL/anti-NgR hydrogels with neural stem cells after culture for 3 days demonstrated a permissive interface with the host tissue without formation of glial scar. These results demonstrate the promise of HA/PLL/anti-NgR hydrogels as potential synthetic cell carriers for transplantation of neural stem cells.