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

Fan Yang, Yunhui Liu, Jie Tu, Jun Wan, Jie Zhang, Bifeng Wu, Shanping Chen, Jiawei Zhou, Yangling Mu & Liping Wang

Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

Nature Communications

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.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)

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