Combination of Adult Mesenchymal Stem Cell Therapy and Immunomodulation with Dimethyl Fumarate Following Spinal Cord Ventral Root Repair

Biology, 2024 · DOI: 10.3390/biology13110953 · Published: November 20, 2024

Spinal Cord Injury Regenerative Medicine Immunology

Simple Explanation

Spinal cord injury affects millions of individuals worldwide, underscoring the urgent need for more effective treatments that can facilitate the recovery of motor and sensory functions. The present study demonstrates that the combination of dimethyl fumarate, an immunomodulatory drug, with adult mesenchymal stem cells derived from adipose tissue exhibits neuroprotective and immunomodulatory properties. The collective findings support the potential of integrated regenerative strategies following spinal cord root injury.

Study Duration

12 weeks postoperative survival period

Participants

115 eight-week-old young adult female Lewis rats

Evidence Level

Not specified

Key Findings

1
The combined therapy resulted in a reduced glial response and a 70% improvement in behavioral motor recovery.
2
AT-MSC treatment significantly preserved general synapses in the lesion microenvironment (78%).
3
Significant motoneuron degeneration was found in the VRR group, with 44% of neurons being preserved. In contrast, both groups treated with AT-MSCs showed improved outcomes, demonstrating 57% preservation in the VRR + AT-MSC group and 63% in the group with all therapeutic approaches (VRR + AT-MSC + DMF).

Research Summary

This study investigated the efficiency of combining heterologous fibrin biopolymer (HFB) for reimplantation, mesenchymal stem cell (MSC) therapy, and dimethyl fumarate (DMF) administration in treating experimental ventral root avulsion in a rat model. AT-MSCs exhibited superior synaptic preservation, which places them as the preferred choice for subsequent experiments for the study of reimplantation with HFB and cell therapy in combination with DMF treatment. The combination of therapeutic strategies involving pharmacological treatment, cell therapy, and surgical repair with HFB demonstrated a notably positive impact on gait recovery, persisting until day 84 after the injury.

Practical Implications

Clinical Translation

The study suggests that a combination of root reimplantation with HFB, cell therapy with AT-MSCs, and pharmacological treatment with DMF could be a viable clinical approach after spinal cord injury.

Therapeutic Strategies

The findings reinforce the need for early combined therapeutic strategies in spinal cord injury treatment to enhance neuroprotection, reduce inflammation, and improve functional recovery.

Future Research

The authors emphasize the need for further validation in larger animal models, including primates, before translation to the clinic, suggesting that this preclinical study provides a proof of concept for the combinatorial treatment approach.

Study Limitations

1
The present preclinical study requires further validation in larger animal models, including primates, before translation to the clinic.
2
The use of female rats for ease of handling and CatWalk analysis could be complemented by further evaluation of male response to the same experimental approach.
3
Although we used inbred Lewis rats, there is also the possibility of individual variation in response to injury.

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