Biomimetic microenvironment modulates neural stem cell survival, migration, and differentiation.
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.
Stabenfeldt
Sarah E
SE
Laboratory for Neuroengineering, Coulter Department of Biomedical Engineering, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Emory University, Atlanta, Georgia, USA.
Munglani
Gautam
G
García
Andrés J
AJ
LaPlaca
Michelle C
MC
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds