Activated astrocytes enhance the dopaminergic differentiation of stem cells and promote brain repair through bFGF

Nat Commun. 2014 Dec 17:5:5627. doi: 10.1038/ncomms6627.

Abstract

Astrocytes provide neuroprotective effects against degeneration of dopaminergic (DA) neurons and play a fundamental role in DA differentiation of neural stem cells. Here we show that light illumination of astrocytes expressing engineered channelrhodopsin variant (ChETA) can remarkably enhance the release of basic fibroblast growth factor (bFGF) and significantly promote the DA differentiation of human embryonic stem cells (hESCs) in vitro. Light activation of transplanted astrocytes in the substantia nigra (SN) also upregulates bFGF levels in vivo and promotes the regenerative effects of co-transplanted stem cells. Importantly, upregulation of bFGF levels, by specific light activation of endogenous astrocytes in the SN, enhances the DA differentiation of transplanted stem cells and promotes brain repair in a mouse model of Parkinson's disease (PD). Our study indicates that astrocyte-derived bFGF is required for regulation of DA differentiation of the stem cells and may provide a strategy targeting astrocytes for treatment of PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Astrocytes / metabolism
  • Astrocytes / radiation effects
  • Astrocytes / transplantation
  • Cell Differentiation
  • Cell- and Tissue-Based Therapy / methods*
  • Cells, Cultured
  • Disease Models, Animal
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Gene Expression Regulation
  • Humans
  • Light
  • Mice
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology
  • Neurogenesis / genetics
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Parkinson Disease / therapy*
  • Protein Engineering
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Rhodopsin / genetics
  • Rhodopsin / metabolism
  • Stem Cell Transplantation*
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology

Substances

  • Recombinant Proteins
  • Fibroblast Growth Factor 2
  • Rhodopsin