The Efﬁciency of Neurospheres Derived from Human Wharton’s Jelly Mesenchymal Stem Cells for Spinal Cord Injury Regeneration in Rats

Int. J. Mol. Sci., 2023 · DOI: 10.3390/ijms24043846 · Published: February 14, 2023

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Spinal cord injury (SCI) leads to inflammation and nerve cell damage, causing loss of movement. Stem cell therapy is being explored as a treatment option. This study investigated using human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) to create neural stem/progenitor cells in sphere form, called neurospheres. The researchers induced hWJ-MSCs into neurospheres using molecules (P7C3 and Isx9) that enhance nerve cell development. These neurospheres were then transplanted into rats with SCI to see if they could help recovery. The best neurosphere type was chosen based on its characteristics for transplantation. The results showed that neurospheres induced with Isx9 could help rats with SCI regain movement. The transplanted cells were found in the injured spinal cord tissue and showed signs of nerve activity. The rats that received neurospheres also had less cavity formation in the injured area, suggesting tissue recovery.

Study Duration

8 weeks

Participants

50 Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Neurospheres induced by 10 µM Isx9 for 7 days produced neural stem/progenitor cell markers such as Nestin and β-tubulin 3 through the Wnt3A signaling pathway regulation markers (β-catenin and NeuroD1 gene expression).
2
Rats transplanted with the neurospheres could move normally, as shown by behavioral tests eight weeks after transplantation.
3
Neurosphere-transplanted rats showed the lowest cavity size of the SCI tissue resulting from the injury recovery mechanism.

Research Summary

This study aimed to induce hWJ-MSCs into neural stem/progenitor cells in sphere formation (neurospheres) by using neurogenesis-enhancing small molecules (P7C3 and Isx9) and transplant to recover an SCI in a rat model. In conclusion, hWJ-MSCs could differentiate into neurospheres using 10 µM Isx9 media through the Wnt3A signaling pathway. The locomotion and tissue recovery of the SCI rats with neurosphere transplantation were better than those without transplantation.

Practical Implications

Potential SCI Treatment

hWJ-MSCs differentiated into neurospheres show promise as a potential cell therapy for spinal cord injury.

Drug Target Identification

Isx9 promotes neurosphere differentiation and SCI recovery, indicating it as a potential drug target.

Wnt3A Signaling Pathway

The Wnt3A signaling pathway is critical for neurosphere differentiation and SCI recovery, offering insights for targeted therapies.

Study Limitations

1
Specific inhibitor markers should be further examined after NSs differentiation for more data support to the Wnt3A signaling pathway.
2
More frequent examination of the pathology and histology at different periods of the SCI model is suggested.
3
A more detailed understanding of the mechanism of the improvement can be concluded.

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