Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

Biomolecules, 2019 · DOI: 10.3390/biom9120811 · Published: December 1, 2019

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Mesenchymal stem cells (MSCs) are promising for tissue regeneration due to their ability to migrate to injury sites and promote immunomodulatory, antiapoptotic, and anti-inflammatory effects. This study compares the effectiveness of MSCs from different sources (bone marrow, adipose tissue, and dental pulp) in treating spinal cord injury (SCI) in rats and pigs. The research indicates that adipose-derived MSCs (AD-MSCs) combined with a fibrin matrix show greater potential for nerve tissue regeneration after SCI in both rats and pigs during the subacute phase.

Study Duration

11 weeks (rats), 22 weeks (pigs)

Participants

115 rats, 17 pigs

Evidence Level

Level 3; Animal Studies

Key Findings

1
In rats, AD-MSCs significantly improved locomotor activity, nerve conduction, reduced tissue damage, and modulated immune cell activation compared to bone marrow or dental pulp MSCs.
2
In pigs, AD-MSCs partially restored somatosensory pathways, reduced tissue damage, and modulated immune cell activation, although the effects were not as pronounced as in rats.
3
AD-MSCs application led to the largest increase in mRNA expression of Fgf2 and application of DP-MSCs lead to the largest increase in Vegf (p < 0.05), compared to other experimental groups.

Research Summary

This study comparatively assesses the therapeutic potential of mesenchymal stem cells (MSCs) from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) in rat and pig models of spinal cord injury (SCI). The findings suggest that AD-MSCs combined with fibrin matrix during the subacute phase of SCI in rats lead to significantly higher post-traumatic regeneration compared to BM-MSCs or DP-MSCs. While AD-MSCs showed positive effects in pigs, including partial restoration of somatosensory pathways and tissue retention, the results were not as robust as those observed in rats, highlighting potential differences in regenerative capacity between small and large animal models.

Practical Implications

Clinical Translation Potential

AD-MSCs, due to their ease of isolation and consistent proliferative activity, represent a promising cell source for clinical translation in treating subacute SCI.

Combination Therapy

The combined application of AD-MSCs with a fibrin matrix could provide a safe and effective approach for cell transplantation in humans with SCI.

Further Research

Further research is needed to analyze the secretory phenotype of donor cells to confirm how the therapeutic activity of transplanted MSCs is mediated before clinical translation.

Study Limitations

1
The mechanisms behind the superior therapeutic effect of AD-MSCs compared to BM-MSCs or DP-MSCs require further investigation.
2
Donor-related heterogeneity of MSCs can lead to significant differences in the secretory phenotype and neuroregenerative potential.
3
The study highlights potential differences in neuroregenerative capacity between small and large animals, necessitating careful consideration in translational studies.

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