Signiﬁcant Therapeutic Effects of Adult Human Neural Stem Cells for Spinal Cord Injury Are Mediated by Monocyte Chemoattractant Protein-1 (MCP-1)

International Journal of Molecular Sciences, 2022 · DOI: 10.3390/ijms23084267 · Published: April 12, 2022

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates the potential of adult human neural stem cells (ahNSCs) derived from focal cortical dysplasia (FCD) type IIIa to treat spinal cord injury (SCI). The research aims to understand how these cells can aid in recovery and identify the mechanisms involved. The results showed that transplanting ahNSCs improved motor functions and nerve fiber regeneration in damaged spinal cord regions. Additionally, the neuroprotective effects of ahNSCs were linked to the inhibition of apoptosis (cell death) in spinal cord neurons. The study identified monocyte chemoattractant protein-1 (MCP-1) as a key paracrine mediator released from ahNSCs. This protein plays a crucial role in the neuroprotective effects observed, suggesting its importance in the therapeutic action of ahNSCs.

Study Duration

Not specified

Participants

Sprague-Dawley rats (female)

Evidence Level

Not specified

Key Findings

1
Transplantation of ahNSCs significantly improved motor function recovery in SCI animal models, with higher BBB scores observed in medium and high dosage groups compared to the vehicle group.
2
The neuroprotective effects of ahNSCs in SCI were mediated by inhibiting apoptosis of spinal cord neurons, as evidenced by reduced TUNEL-positive apoptotic cells and decreased cleaved caspase 3-positive neurons in the ahNSCs transplanted group.
3
Monocyte chemoattractant protein-1 (MCP-1) was identified as a key paracrine mediator released from ahNSCs, contributing to the neuroprotective effects. Blocking MCP-1 with a neutralizing antibody reversed the neuroprotective effects of ahNSCs CM.

Research Summary

The study aimed to characterize the therapeutic effects of adult human neural stem cells (ahNSCs) derived from focal cortical dysplasia type IIIa for spinal cord injury (SCI) and elucidate their treatment mechanisms. Results showed that ahNSCs transplantation significantly improved motor functions and nerve fiber regeneration in damaged spinal cord regions, mediated by inhibiting apoptosis of spinal cord neurons. Monocyte chemoattractant protein-1 (MCP-1) was identified as a key paracrine mediator released from ahNSCs, contributing to the neuroprotective effects observed, suggesting its importance in the therapeutic action of ahNSCs.

Practical Implications

Cell Therapeutics Development

The results encourage the further preclinical and clinical development of effective and safe cell therapeutics for SCI, addressing the current lack of available therapeutic options.

Therapeutic Target Identification

MCP-1 may be a key therapeutic target for SCI treatment, suggesting potential strategies to enhance neuroprotection and anti-apoptosis in SCI animal models.

Clinical Translation

ahNSCs from neurological disorders might be utilized to develop cell therapeutics for SCI.

Study Limitations

1
Differences in the treatment effects among the treated groups might have resulted from the number of ahNSCs that migrated into the lesions of spinal cords, which needs to be determined further.
2
In vitro experiments are not enough to explain the in vivo roles of MCP-1 in the treatment effects of ahNSCs.
3
In vivo experiments using neutralizing antibodies against MCP-1 and/or speciﬁc shRNAs for MCP-1 should be required in future studies.

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