Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells From Different Donors on Spinal Cord Injury in Mice

Frontiers in Cellular Neuroscience, 2022 · DOI: 10.3389/fncel.2021.768711 · Published: January 11, 2022

Simple Explanation

Spinal cord injury (SCI) often leads to limb dysfunction, with inflammation playing a significant role in its prognosis. Transplanting human umbilical cord mesenchymal stem cells (hUCMSCs) can aid SCI repair by lessening inflammation. This study investigates how different lines of hUCMSCs affect SCI in mice, examining hind limb motor function, tissue samples, protein levels, gene expression, and RNA sequencing to understand the mechanisms involved. The study suggests that the effectiveness of hUCMSC transplantation in acute SCI depends on their ability to inhibit the inflammatory response after nerve injury. This finding could inform future clinical applications of hUCMSCs.

Study Duration

6 weeks

Participants

156 adult female C57 mice

Evidence Level

Not specified

Key Findings

1
The therapeutic effects of hUCMSC lines were positively correlated with their inhibitory abilities on BV2 cell proliferation rates in vitro, indicating that more potent anti-inflammatory hUCMSCs led to better outcomes.
2
MSC_A line significantly improved hind limb motor function and had a greater effect on reducing the expression of glial fibrillary acidic protein (Gfap) and ionized calcium binding adaptor molecule 1 (Iba1), while increasing neuronal nuclei (NeuN) expression.
3
Differentially expressed genes including Zbtb16, Per3, and Hif3a were identified as potentially key to the protective mechanism of MSC_A after nerve injury, with qRT-PCR verifying that MSC_A application reversed the SCI-induced reduction in their expression.

Research Summary

This study investigates the neuroprotective effects of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) from different donors on spinal cord injury (SCI) in mice. The findings indicate that the therapeutic effects of hUCMSCs are positively correlated with their inhibitory abilities on BV2 cell proliferation in vitro, with MSC_A demonstrating superior improvement in hind limb motor function and modulation of key protein expressions. The study identifies Zbtb16, Per3, and Hif3a as key genes involved in the protective mechanism of MSC_A after nerve injury, suggesting that hUCMSC transplantation for acute SCI depends on their inhibitory abilities to inflammation reaction.

Practical Implications

Personalized Stem Cell Therapy

The study highlights the importance of selecting hUCMSC lines with high anti-inflammatory capabilities for SCI treatment, suggesting a need for personalized stem cell therapy approaches.

Targeted Gene Therapy

Identifying Zbtb16, Per3, and Hif3a as key genes opens avenues for targeted gene therapy to enhance the neuroprotective effects of stem cell transplantation.

Optimized Timing of Transplantation

The finding that hUCMSC transplantation at dpo 3 yields better outcomes than at dpo 1 or wpo 2 suggests an optimal time window for intervention to maximize therapeutic benefits.

Study Limitations

1
The study was conducted on mice, and the results may not directly translate to humans.
2
The exact mechanisms by which Zbtb16, Per3, and Hif3a contribute to neuroprotection require further investigation.
3
The long-term effects of hUCMSC transplantation on SCI were not assessed in this study.

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