Three-dimensional self-organizing neural architectures: A neural stem cells reservoir and a system for neurodevelopmental studies

Silvia Cristini, Giulio Alessandri, Francesco Acerbi, Emilio Ciusani, Augusto Colombo, Umberto Fascio, Roberto F. Nicosia, Roberto W. Invernizzi, Maurizio Gelati, Eugenio A. Parati, Gloria Invernici

Research output: Contribution to journalArticlepeer-review


Complex microenvironmental stimuli influence neural cell properties. To study this, we developed a three-dimensional (3-D) neural culture system, composed of different populations including neurons, astrocytes, and neural stem cells (NSCs). In particular, these last-mentioned cells represent a source potentially exploitable to test drugs, to study neurodevelopment and cell-therapies for neuroregenerations. On seeding on matrigel in a medium supplemented with serum and mitogens, cells obtained from human fetal brain tissue formed 3-D self-organizing neural architectures. Immunocytochemical analysis demonstrated the presence of undifferentiated nestin+ and CD133+ cells, surrounded by β-tub-III+ and GFAP+ cells, suggesting the formation of niches containing potential human NSCs (hNSCs). The presence of hNSCs was confirmed by both neurosphere assay and RT-PCR, and their multipotentiality was demonstrated by both immunofluorescent staining and RT-PCR. Flow cytometry analysis revealed that neurosphere forming cells originating from at least two different subsets expressing, respectively, CD133 and CD146 markers were endowed with different proliferative and differentiation potential. Our data implicate that the complexity of environment within niches and aggregates of heterogeneous neural cell subsets may represent an innovative platform for neurobiological and neurodevelopmental investigations and a reservoir for a rapid expansion of hNSCs.

Original languageEnglish
Pages (from-to)1109-1120
Number of pages12
JournalTissue Engineering - Part C: Methods
Issue number11
Publication statusPublished - Nov 1 2011

ASJC Scopus subject areas

  • Biomedical Engineering
  • Bioengineering
  • Medicine (miscellaneous)
  • Medicine(all)


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