Biomimetic Microenvironment Modulates Neural Stem Cell Survival, Migration, and Differentiation

Abstract

Biomaterial matrices presenting extracellular matrix (ECM) components in a controlled three-dimensional configuration provide a unique system to study neural stem cell (NSC)-ECM interactions. We cultured primary murine neurospheres in a methylcellulose (MC) scaffold functionalized with laminin-1 (MC-x-LN1) and monitored NSC survival, apoptosis, migration, differentiation, and matrix production. Overall, MC-x-LN1 enhanced both NSC survival and maturation compared with MC controls. Significantly lower levels of apoptotic activity were observed in MC-x-LN1 than in MC controls, as measured by bcl-2/bax gene expression and tetramethylrhodamine-dUTP nick end labeling. A higher percentage of NSCs extended neurites in a β₁-integrin-mediated fashion in MC-x-LN1 than in MC controls. Further, the differentiation profiles of NSCs in MC-x-LN1 exhibited higher levels of neuronal and oligodendrocyte precursor markers than in MC controls. LN1 production and co-localization with α₆β₁ integrins was markedly increased within MC-x-LN1, whereas the production of fibronectin was more pronounced in MC controls. These findings demonstrate that NSC microenvironments modulate cellular activity throughout the neurosphere, contributing to our understanding of ECM-mediated NSC behavior and provide new avenues for developing rationally designed couriers for neurotransplantation.

Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers

“…13,20 Furthermore, it is well-known that extracellular matrix (ECM) components play a role in the differentiation of NSCs into neurons. 29,30 Our data showed that the rate of Map2-positive cells was higher in the PLGA-SF group than in the PLGA-only group. These results not only demonstrated the known function of NT-3 in neuronal survival and differentiation, but also suggested that SF may contribute to the differentiation of neurons.…”

Oriented, Multimeric Biointerfaces of the L1 Cell Adhesion Molecule: An Approach to Enhance Neuronal and Neural Stem Cell Functions on 2-D and 3-D Polymer Substrates

“…Biointerfacial display of neurotrophic factors has the potential to significantly influence neural cell behaviors relevant to CNS repair, including adhesion, differentiation, and neurite extension [51,52]. In this study, we investigated multiple presentation schemes for the neural cell adhesion molecule L1 to elucidate the effects of presentation on primary neurons and human embryonic stem cellderived NPCs on 2-D and 3-D polymer substrates.…”

Harnessing the Potential of Biomaterials for Brain Repair after Stroke

“…NPCs express the major integrin for laminin, α6β1, which promotes differentiation of hESCs to neurons in vitro (Ma et al, 2008;Stabenfeldt et al, 2010). When collagen I hydrogels containing fibronectin or laminin were compared for delivery of fetal-derived NSCs, laminin-containing gels resulted in increased cell survival 8 weeks posttransplantation compared to those with fibronectin (Tate et al, 2009).…”