Effects of FGF2 Priming and Nrf2 Activation on the Antioxidant Activity of Several Human Dental Pulp Cell Clones Derived From Distinct Donors, and Therapeutic Effects of Transplantation on Rodents With Spinal Cord Injury

Cell Transplantation, 2024 · DOI: 10.1177/09636897241264979 · Published: June 12, 2024

Spinal Cord Injury Regenerative Medicine

Simple Explanation

This study investigates the therapeutic potential of human dental pulp cells (DPCs) for spinal cord injury (SCI) treatment. It highlights individual cellular characteristic differences of human DPC clones and their therapeutic efficacy in rodent SCI models. The research aims to clarify which cellular properties are associated with their therapeutic efficacy for SCI. The study examines the effects of basic fibroblast growth factor 2 (FGF2) and bardoxolone methyl (RTA402), an Nrf2 activator, on the antioxidant capacity and resistance to H2O2 cytotoxicity in DPCs. The goal is to enhance DPCs' ability to survive and function in the harsh environment of an injured spinal cord. The findings suggest that combining FGF2 and RTA402 treatments can improve DPCs' antioxidant activity and cytoprotective effects, potentially increasing their therapeutic efficacy for SCI. This combination may help transplanted DPCs migrate to the injury site and secrete neurotrophic factors, promoting recovery.

Study Duration

7 weeks (rats), 5 weeks (mice)

Participants

Human dental pulp cells (DPCs) from seven different donors, 57 female rats, 75 female mice

Evidence Level

Not specified

Key Findings

1
FGF2 priming enhances the resistance of a subset of DPC clones to H2O2 cytotoxicity.
2
RTA402 markedly enhances the resistance of many DPC clones to H2O2 cytotoxicity, concomitant with the upregulation of HO-1 and NQO1.
3
Combined FGF2 priming and RTA402 treatment significantly upregulated the TAC in each DPC clone.

Research Summary

The study examined the effects of FGF2 priming and Nrf2 activation on the antioxidant activity of human dental pulp cells (DPCs) and their therapeutic effects on spinal cord injury (SCI) in rodents. The findings indicate that RTA402 treatment enhances cellular resistance to H2O2 cytotoxicity via the upregulation of HO-1 and NQO1 proteins, with FGF2 priming improving growth and migration of DPC clones. The transplantation of DPCs pre-treated with FGF2/RTA402 promoted the regeneration of 5-HT+-nerve fibers and improved locomotor function in SCI model mice.

Practical Implications

Improved SCI Therapy

Combining FGF2 and RTA402 may improve the effectiveness of DPC transplantation for SCI by enhancing antioxidant activity and reducing clonal variability.

Personalized Medicine

Considering individual DPC properties and patient-specific factors can lead to more effective cell transplantation therapies.

Allogeneic Transplantation

Using HHH DPC clones with high antioxidant activity and therapeutic efficacy could be a viable approach for SCI treatment.

Study Limitations

1
The number of 5-HT+-nerve fibers was small and insufficient to contribute to the recovery of coordinated movements.
2
The study is limited by clonal differences in DPCs, requiring further investigation into the underlying mechanisms.
3
The need for optimization in administration route and dosing strategies.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury