Novel therapeutic approach to slow down the inﬂammatory cascade in acute/subacute spinal cord injury: Early immune therapy with lipopolysaccharide enhanced neuroprotective effect of combinational therapy of granulocyte colony-stimulating factor and bone-marrow mesenchymal stem cell in spinal cord injury

Frontiers in Cellular Neuroscience, 2022 · DOI: 10.3389/fncel.2022.993019 · Published: November 23, 2022

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This study investigates a novel therapeutic approach for acute/subacute spinal cord injury (SCI) focusing on slowing down the inflammatory cascade. The approach involves early immune therapy using lipopolysaccharide (LPS) to enhance the neuroprotective effect of a combination therapy. The combinational therapy consists of granulocyte colony-stimulating factor (G-CSF) and bone-marrow mesenchymal stem cells (BM-MSCs).

Study Duration

5-6 Weeks

Participants

Adult male Wistar rats (weighing 260 ± 10 g)

Evidence Level

Not specified

Key Findings

1
Medium-dose LPS administration resulted in a local anti-inflammatory beneficial role, associated with increased NF-200-positive cells, tissue sparing, and improved functional recovery.
2
Combination therapy (LPS + G-CSF) enhanced the anti-inflammatory response (IL-10 and Arg-1) and decreased inflammatory markers (TNF-α and CD86) and caspase-3 compared to BM-MSC monotherapy.
3
Combination groups displayed better structural remodeling than BM-MSC monotherapy, and drug therapy showed faster recovery than BM-MSC monotherapy.

Research Summary

This study aimed to modulate the inflammatory milieu in spinal cord injury (SCI) by using lipopolysaccharide (LPS) and granulocyte colony-stimulating factor (G-CSF) to improve bone-marrow mesenchymal stem cells (BM-MSCs) therapy. The results suggest that a sub-toxic dose of LPS provides neuroprotection to SCI and can promote the beneficial effect of BM-MSC in SCI. The findings indicate that a combination of LPS or LPS + G-CSF prior to BM-MSC transplantation is a promising approach for optimizing BM-MSC-based strategies to treat SCI.

Practical Implications

Optimizing BM-MSC Therapy

Combining LPS or LPS + G-CSF with BM-MSC transplantation may optimize BM-MSC-based strategies for SCI treatment.

Neuroprotection via LPS

A sub-toxic dose of LPS may provide neuroprotection in SCI.

Anti-Inflammatory Modulation

Modulating the inflammatory response using LPS and G-CSF can create a more permissive environment for cell transplantation in SCI.

Study Limitations

1
Lack of some methodological considerations to examine the survival rate and ultimate fate of transplanted BM-MSCs followed by LPS administration
2
The presence of only one-time point for evaluating the inflammatory response (1 week) after SCI
3
Inclusion of additional time points would provide more information about the effect of our combination therapy on the microglia/macrophage polarization dynamic at the injured spinal cord.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury