The enhancement of CCL2 and CCL5 by human bone marrow-derived mesenchymal stem/stromal cells might contribute to inflammatory suppression and axonal extension after spinal cord injury

PLoS ONE, 2020 · DOI: https://doi.org/10.1371/journal.pone.0230080 · Published: March 10, 2020

Spinal Cord Injury Regenerative Medicine Immunology

Simple Explanation

Human bone marrow-derived mesenchymal stem/stromal cells (hMSCs) have shown potential in facilitating recovery from spinal cord injury (SCI) through communicating with microglia/macrophages (MG/MΦ). This study focuses on chemokines, specifically CCL2/CCR2 and CCL5/CCR5, as mediators of this communication. The research investigates how hMSC transplantation affects the expression of these chemokines, inflammation, MG/MΦ polarization, and axonal regeneration in a mouse model of SCI.

Study Duration

14 days

Participants

139 male C57/BL6 mice

Evidence Level

Not specified

Key Findings

1
hMSC transplantation enhanced Ccl2 and Ccl5 expression and improved locomotor activity in mice with SCI.
2
hMSC implantation decreased the expression of inflammatory markers Il1, Elane, and Mpo on pod 3 (postoperative day 3).
3
hMSC transplantation increased expression of Zc3h12a (encodes MCP-1-induced protein), Aif1, Arg1 and Chil3 (Ym1), as well as axonal regenerative markers, Dpysl2 and Gap43.

Research Summary

This study investigates the effects of human mesenchymal stem/stromal cells (hMSCs) on spinal cord injury (SCI) recovery in mice, focusing on the roles of chemokines CCL2/CCR2 and CCL5/CCR5. The researchers found that hMSC transplantation enhances Ccl2 and Ccl5 expression, improves locomotor activity, and promotes MG/MΦ polarization to AAM (alternatively activated macrophage). These functions of hMSCs might be partially mediated by the CCL2/CCR2 and CCL5/CCR5 axes, contributing to inflammatory suppression and axonal extension after SCI.

Practical Implications

Therapeutic Potential

hMSCs may offer a therapeutic avenue for SCI by modulating chemokine expression and promoting tissue repair.

Chemokine Targeting

Targeting CCL2/CCR2 and CCL5/CCR5 axes could enhance the efficacy of hMSC-based therapies.

Inflammation Control

hMSC transplantation can suppress inflammation and promote axonal regeneration in SCI.

Study Limitations

1
The study was conducted on mice, and results may not directly translate to humans.
2
The precise mechanisms by which hMSCs communicate with recipient tissues remain to be fully elucidated.
3
Further research is needed to determine the long-term effects of hMSC transplantation on SCI recovery.

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