Biomimetic microenvironment modulates neural stem cell survival, migration, and differentiation

Sarah E. Stabenfeldt, Gautam Munglani, Andrés J. García, Michelle C. Laplaca

Research output: Contribution to journalArticle

57 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3747-3758
Number of pages12
JournalTissue Engineering - Part A
Volume16
Issue number12
DOIs
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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