Transplantation of neural stem cells preconditioned with high-mobility group box 1 facilitates functional recovery after spinal cord injury in rats

Molecular Medicine Reports, 2020 · DOI: 10.3892/mmr.2020.11565 · Published: July 6, 2020

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Spinal cord injury (SCI) is a devastating disorder that often results in temporary and/or permanent functional impairment below the injured level. Cell transplantation therapy, particularly using neuronal stem cells (NSCs), is being explored as a promising therapeutic strategy. Preconditioning NSCs with specific substances, like high mobility group box-1 (HMGB1), can improve their survival and effectiveness after transplantation. This study investigates whether preconditioning NSCs with HMGB1 can improve functional recovery after SCI in rats. The researchers examined the effects of transplanting HMGB1-preconditioned NSCs on motor function, pain sensitivity, and tissue regeneration in rats with SCI. The results suggest that transplanting NSCs preconditioned with HMGB1 can facilitate functional improvement of injured spinal cords, reduce tissue atrophy, and increase the number of functional neurons at the injury site. This preconditioning strategy may be a feasible approach for cell-based therapy following SCI.

Study Duration

Not specified

Participants

60 male SD rats and 8 embryonic day 14.5 (E14.5) SD rats

Evidence Level

Not specified

Key Findings

1
Transplantation of NSCs preconditioned with 1 ng/ml HMGB1 facilitated functional improvement of injured spinal cords, as indicated by improved Basso, Beattie and Bresnahan mean scores, reduced mechanical hypersensitivity, and decreased cold stimulation response.
2
Engraftment of HMGB1-preconditioned NSCs resulted in decreased atrophy of the injured spinal cord and an increased number of functional Nissl bodies in neurons, indicating improved neuronal survival.
3
HMGB1 promoted the differentiation of NSCs into neurons, and the ERK signaling pathway played an important role in this process, suggesting a potential mechanism for the observed functional improvements.

Research Summary

This study investigates the potential of using neural stem cells (NSCs) preconditioned with high mobility group box-1 (HMGB1) to improve functional recovery after spinal cord injury (SCI) in rats. The researchers hypothesized that HMGB1 preconditioning could enhance NSC survival and differentiation, leading to better outcomes after transplantation. The findings indicate that transplanting HMGB1-preconditioned NSCs resulted in improved locomotor recovery, reduced pain sensitivity, decreased spinal cord atrophy, and increased neuronal survival in rats with SCI. These effects were associated with HMGB1-induced differentiation of NSCs into neurons, potentially mediated by the ERK signaling pathway. The study concludes that HMGB1 preconditioning is a feasible strategy for optimizing cell replacement therapy using NSCs for SCI, offering a potential avenue for future therapeutic development.

Practical Implications

Therapeutic Potential for SCI

HMGB1 preconditioning of NSCs can be further explored as a cell-based therapy to improve functional recovery in SCI patients.

Mechanism Elucidation

Further research can focus on fully understanding the underlying mechanisms by which HMGB1 promotes NSC differentiation and neuronal survival, particularly the role of the ERK signaling pathway.

Optimization of Transplantation

Future studies should investigate optimal administration routes, timing of transplantation, and NSC-specific markers to provide more evidence for HMGB1-facilitated NSC differentiation.

Study Limitations

1
The method of administrating HMGB1‑preconditioned NSCs, such as via intravenous injection.
2
The ideal time point of HMGB1‑preconditioned NSC engraftment.
3
A more appropriate time point for the sampling measurements (immunostaining and western blotting), instead of day 21

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