Multifunctionalized hydrogels foster hNSC maturation in 3D cultures and neural regeneration in spinal cord injuries

Amanda Marchini, Andrea Raspa, Raffaele Pugliese, Marina Abd El Malek, Valentina Pastori, Marzia Lecchi, Angelo L. Vescovi, Fabrizio Gelain

Research output: Contribution to journalArticle

Abstract

Three-dimensional cell cultures are leading the way to the fabrication of tissue-like constructs useful to developmental biology and pharmaceutical screenings. However, their reproducibility and translational potential have been limited by biomaterial and culture media compositions, as well as cellular sources. We developed a construct comprising synthetic multifunctionalized hydrogels, serum-free media, and densely seeded good manufacturing practice protocol-grade human neural stem cells (hNSC). We tracked hNSC proliferation, differentiation, and maturation into GABAergic, glutamatergic, and cholinergic neurons, showing entangled electrically active neural networks. The neuroregenerative potential of the “engineered tissue” was assessed in spinal cord injuries, where hNSC-derived progenitors and predifferentiated hNSC progeny, embedded in multifunctionalized hydrogels, were implanted. All implants decreased astrogliosis and lowered the immune response, but scaffolds with predifferentiated hNSCs showed higher percentages of neuronal markers, better hNSC engraftment, and improved behavioral recovery. Our hNSC-construct enables the formation of 3D functional neuronal networks in vitro, allowing novel strategies for hNSC therapies in vivo.

Original languageEnglish
Pages (from-to)7483-7492
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number15
DOIs
Publication statusPublished - Apr 9 2019

Keywords

  • 3D cell cultures
  • Nervous tissue engineering
  • Neural stem cells
  • Self-assembling peptides
  • Spinal cord injury

ASJC Scopus subject areas

  • General

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