Polydatin promotes the neuronal differentiation of bone marrow mesenchymal stem cells in vitro and in vivo: Involvement of Nrf2 signalling pathway

J Cell Mol Med, 2020 · DOI: 10.1111/jcmm.15187 · Published: May 1, 2020

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This study investigates the potential of polydatin (PD), a component of a Chinese herb, to enhance the ability of bone marrow mesenchymal stem cells (BMSCs) to differentiate into neurons, both in lab settings and in a mouse model of spinal cord injury (SCI). The researchers found that PD facilitates BMSC differentiation into neuron-like cells by activating the Nrf2 pathway, a key regulator of cellular response to oxidative stress. The study also showed that combining PD with BMSC transplantation promotes axonal rehabilitation, reduces glial scar formation, and enhances the recovery of hindlimb locomotor function in mice with SCI, suggesting a promising therapeutic approach.

Study Duration

Not specified

Participants

150 mice (20-25 g)

Evidence Level

Level 1: Experimental study using animal model

Key Findings

1
PD markedly facilitated BMSC differentiation into neuron-like cells by activating the Nrf2 pathway and increased the expression of neuronal markers in the transplanted BMSCs at the injured spinal cord sites.
2
The combination of PD and BMSC transplantation promoted axonal rehabilitation, attenuated glial scar formation and promoted axonal generation across the glial scar, thereby enhancing recovery of hindlimb locomotor function.
3
PD augments the neuronal differentiation of BMSCs in the injured spinal cord and aids in functional recovery of the BMSC-treated mice via the Nrf2 signalling pathway.

Research Summary

This study demonstrates that polydatin (PD) enhances the neuronal differentiation of bone marrow mesenchymal stem cells (BMSCs) both in vitro and in vivo, particularly promoting their differentiation into cholinergic neurons. PD, in combination with BMSC transplantation, significantly improves axonal regeneration, reduces glial scar formation, and enhances functional recovery in a mouse model of spinal cord injury (SCI). The beneficial effects of PD are mediated through the activation of the Nrf2 signaling pathway, which plays a crucial role in neuronal differentiation and resistance to oxidative stress.

Practical Implications

Therapeutic Strategy for SCI

The combination of PD and BMSC transplantation presents a promising new therapeutic approach against SCI, by enhancing neuronal differentiation and functional recovery.

Nrf2 Activation

Activation of the Nrf2 signaling pathway is a key mechanism through which PD promotes neuronal differentiation and improves outcomes in SCI.

Cholinergic Motor Neuron Differentiation

PD enhances the therapeutic effect of BMSCs by facilitating their differentiation into cholinergic motor neurons, which are pivotal for locomotion and behavioral responses.

Study Limitations

1
The precise molecular mechanisms controlling neuronal differentiation are highly complex and involve multiple signalling pathways.
2
PD alone cannot initiate the differentiation of BMSCs.
3
Further research is needed to fully elucidate the long-term effects and potential side effects of PD and BMSC transplantation in SCI treatment.

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