Neuronal differentiation and functional maturation of neurons from neural stem cells induced by bFGF-chitosan controlled release system

Drug Deliv Transl Res. 2023 Sep;13(9):2378-2393. doi: 10.1007/s13346-023-01322-x. Epub 2023 Mar 21.

Abstract

Available methods for differentiating stem cells into neurons require a large number of cytokines and neurotrophic factors, with complex steps and slow processes, and are inefficient to produce functional neurons and form synaptic contacts, which is expensive and impractical in clinical application. Here, we demonstrated a bioactive material, basic fibroblast growth factor (bFGF)-chitosan controlled release system, for facilitating neuronal differentiation from NSCs and the functional maturation of the induced neurons with high efficiency. We illustrated by immunostaining that the neurons derived from NSCs expressed mature immunomarkers of interneurons and excitatory neurons. And we found by patch-clamp that the induced neurons exhibited diverse electrophysiological properties as well as formed functional synapses. In vivo, we implanted bFGF-chitosan into lesion area in traumatic brain injury (TBI) mice and similarly observed abundance of neuroblasts in SVZ and the presence of newborn functional neurons in injury area, which integrated into synaptic networks. Taken together, our efficient and rapid tissue engineering approach may be a potential method for the generation of functional neuronal lineage cells from stem cells and a therapy of brain injury and disease.

Keywords: Functional maturation; Neural stem cells; Neuronal differentiation; Synaptic circuits; Traumatic brain injury; bFGF-chitosan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Chitosan*
  • Delayed-Action Preparations
  • Fibroblast Growth Factor 2 / metabolism
  • Mice
  • Neural Stem Cells* / metabolism
  • Neurons / metabolism

Substances

  • Chitosan
  • Fibroblast Growth Factor 2
  • Delayed-Action Preparations